Podcast appearances and mentions of nathan pennell

Dr. Nathan Pennell and Dr. Cheryl Czerlanis discuss challenges in lung cancer screening and potential solutions to increase screening rates, including the use of AI to enhance risk prediction and screening processes. Transcript Dr. Nate Pennell: Hello, and welcome to By the Book, a monthly podcast series for ASCO Education that features engaging discussions between editors and authors from the ASCO Educational Book. I'm Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research for the Taussig Cancer Center. I'm also the editor-in-chief for the ASCO Educational Book.  Lung cancer is one of the leading causes of cancer-related mortality worldwide, and most cases are diagnosed at advanced stages where curative treatment options are limited. On the opposite end, early-stage lung cancers are very curable. If only we could find more patients at that early stage, an approach that has revolutionized survival for other cancer types such as colorectal and breast cancer.  On today's episode, I'm delighted to be joined by Dr. Cheryl Czerlanis, a professor of medicine and thoracic medical oncologist at the University of Wisconsin Carbone Cancer Center, to discuss her article titled, "Broadening the Net: Overcoming Challenges and Embracing Novel Technologies in Lung Cancer Screening." The article was recently published in the ASCO Educational Book and featured in an Education Session at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Cheryl, it's great to have you on the podcast today. Thanks for being here. Dr. Cheryl Czerlanis: Thanks, Nate. It's great to be here with you. Dr. Nate Pennell: So, I'd like to just start by asking you a little bit about the importance of lung cancer screening and what evidence is there that lung cancer screening is beneficial. Dr. Cheryl Czerlanis: Thank you. Lung cancer screening is extremely important because we know that lung cancer survival is closely tied to stage at diagnosis. We have made significant progress in the treatment of lung cancer, especially over the past decade, with the introduction of immunotherapies and targeted therapies based on personalized evaluation of genomic alterations. But the reality is that outside of a lung screening program, most patients with lung cancer present with symptoms related to advanced cancer, where our ability to cure the disease is more limited.  While lung cancer screening has been studied for years, the National Lung Screening Trial, or the NLST, first reported in 2011 a significant reduction in lung cancer deaths through screening. Annual low-dose CT scans were performed in a high-risk population for lung cancer in comparison to chest X-ray. The study population was comprised of asymptomatic persons aged 55 to 74 with a 30-pack-year history of smoking who were either active smokers or had quit within 15 years. The low-dose CT screening was associated with a 20% relative risk reduction in lung cancer-related mortality. A similar magnitude of benefit was also reported in the NELSON trial, which was a large European randomized trial comparing low-dose CT with a control group receiving no screening. Dr. Nate Pennell: So, this led, of course, to approval from CMS (Centers for Medicare and Medicaid Services) for lung cancer screening in the Medicare population, probably about 10 years ago now, I think. And there are now two major trials showing an unequivocal reduction in lung cancer-related mortality and even evidence that it reduces overall mortality with lung cancer screening. But despite this, lung cancer screening rates are very low in the United States. So, first of all, what's going on? Why are we not seeing the kinds of screening rates that we see with mammography and colonoscopy? And what are the barriers to that here? Dr. Cheryl Czerlanis: That's a great question. Thank you, Nate. In the United States, recruitment for lung cancer screening programs has faced numerous challenges, including those related to socioeconomic, cultural, logistical, and even racial disparities. Our current lung cancer screening guidelines are somewhat imprecise and often fail to address differences that we know exist in sex, smoking history, socioeconomic status, and ethnicity. We also see underrepresentation in certain groups, including African Americans and other minorities, and special populations, including individuals with HIV. And even where lung cancer screening is readily available and we have evidence of its efficacy, uptake can be low due to both provider and patient factors. On the provider side, barriers include having insufficient time in a clinic visit for shared decision-making, fear of missed test results, lack of awareness about current guidelines, concerns about cost, potential harms, and evaluating both true and false-positive test results.  And then on the patient side, barriers include concerns about cost, fear of getting a cancer diagnosis, stigma associated with tobacco smoking, and misconceptions about the treatability of lung cancer. Dr. Nate Pennell: I think those last two are really what make lung cancer unique compared to, say, for example, breast cancer, where there really is a public acceptance of the value of mammography and that breast cancer is no one's fault and that it really is embraced as an active way you can take care of yourself by getting your breast cancer screening. Whereas in lung cancer, between the stigma of smoking and the concern that, you know, it's a death sentence, I think we really have some work to be made up, which we'll talk about in a minute about what we can do to help improve this.  Now, that's in the U.S. I think things are probably, I would imagine, even worse when we leave the U.S. and look outside, especially at low- and middle-income countries. Dr. Cheryl Czerlanis: Yes, globally, this issue is even more complex than it is in the United States. Widespread implementation of low-dose CT imaging for lung cancer screening is limited by manpower, infrastructure, and economic constraints. Many low- and middle-income countries even lack sufficient CT machines, trained personnel, and specialized facilities for accurate and timely screenings. Even in urban centers with advanced diagnostic facilities, the high screening and follow-up care costs can limit access. Rural populations face additional barriers, such as geographic inaccessibility of urban centers, transportation costs, language barriers, and mistrust of healthcare systems. In addition, healthcare systems in these regions often prioritize infectious diseases and maternal health, leaving limited room for investments in noncommunicable disease prevention like lung cancer screening. Policymakers often struggle to justify allocating resources to lung cancer screening when immediate healthcare needs remain unmet. Urban-rural disparities exacerbate these challenges, with rural regions frequently lacking the infrastructure and resources to sustain screening programs. Dr. Nate Pennell: Well, it's certainly an intimidating problem to try to reduce these disparities, especially between the U.S. and low- and middle-income countries. So, what are some of the potential solutions, both here in the U.S. and internationally, that we can do to try to increase the rates of lung cancer screening? Dr. Cheryl Czerlanis: The good news is that we can take steps to address these challenges, but a multifaceted approach is needed. Public awareness campaigns focused on the benefits of early detection and dispelling myths about lung cancer screening are essential to improving participation rates. Using risk-prediction models to identify high-risk individuals can increase the efficiency of lung cancer screening programs. Automated follow-up reminders and screening navigators can also ensure timely referrals and reduce delays in diagnosis and treatment. Reducing or subsidizing the cost of low-dose CT scans, especially in low- or middle-income countries, can improve accessibility. Deploying mobile CT scanners can expand access to rural and underserved areas.  On a global scale, integrating lung cancer screening with existing healthcare programs, such as TB or noncommunicable disease initiatives, can enhance resource utilization and program scalability. Implementing lung cancer screening in resource-limited settings requires strategic investment, capacity building, and policy interventions that prioritize equity. Addressing financial constraints, infrastructure gaps, and sociocultural barriers can help overcome existing challenges. By focusing on cost-effective strategies, public awareness, and risk-based eligibility criteria, global efforts can promote equitable access to lung cancer screening and improve outcomes.  Lastly, as part of the medical community, we play an important role in a patient's decision to pursue lung cancer screening. Being up to date with current lung cancer screening recommendations, identifying eligible patients, and encouraging a patient to undergo screening often is the difference-maker. Electronic medical record (EMR) systems and reminders are helpful in this regard, but relationship building and a recommendation from a trusted provider are really essential here. Dr. Nate Pennell: I think that makes a lot of sense. I mean, there are technology improvements. For example, our lung cancer screening program at The Cleveland Clinic, a few years back, we finally started an automated best practice alert in our EMR for patients who met the age and smoking requirements, and it led to a six-fold increase in people referred for screening. But at the same time, there's a difference between just getting this alert and putting in an order for lung cancer screening and actually getting those patients to go and actually do the screening and then follow up on it. And that, of course, requires having that relationship and discussion with the patient so that they trust that you have their best interests. Dr. Cheryl Czerlanis: Exactly. I think that's important. You know, certainly, while technology can aid in bringing patients in, there really is no substitute for trust-building and a personal relationship with a provider. Dr. Nate Pennell: I know that there are probably multiple examples within the U.S. where health systems or programs have put together, I would say, quality improvement projects to try to increase lung cancer screening and working with their community. There's one in particular that you discuss in your paper called the "End Lung Cancer Now" initiative. I wonder if you could take us through that. Dr. Cheryl Czerlanis: Absolutely. "End Lung Cancer Now" is an initiative at the Indiana University Simon Comprehensive Cancer Center that has the vision to end suffering and death from lung cancer in Indiana through education and community empowerment. We discuss this as a paradigm for how community engagement is important in building and scaling a lung cancer screening program.  In 2023, the "End Lung Cancer Now" team decided to focus its efforts on scaling and transforming lung cancer screening rates in Indiana. They developed a task force with 26 experts in various fields, including radiology, pulmonary medicine, thoracic surgery, public health, and advocacy groups. The result of this work is an 85-page blueprint with key recommendations that any system and community can use to scale lung cancer screening efforts. After building strong infrastructure for lung cancer screening at Indiana University, they sought to understand what the priorities, resources, and challenges in their communities were. To do this, they forged strong partnerships with both local and national organizations, including the American Lung Association, American Cancer Society, and others. In the first year, they actually tripled the number of screening low-dose CTs performed in their academic center and saw a 40% increase system-wide. One thing that I think is the most striking is that through their community outreach, they learned that most people prefer to get medical care close to home within their own communities. Establishing a way to support the local infrastructure to provide care became far more important than recruiting patients to their larger system.  In exciting news, "End Lung Cancer Now" has partnered with the IU Simon Comprehensive Cancer Center and IU Health to launch Indiana's first and only mobile lung screening program in March of 2025. This mobile program travels around the state to counties where the highest incidence of lung cancer exists and there is limited access to screening. The mobile unit parks at trusted sites within communities and works in partnership, not competition, with local health clinics and facilities to screen high-risk populations. Dr. Nate Pennell: I think that sounds like a great idea. Screening is such an important thing that it doesn't necessarily have to be owned by any one particular health system for their patients. I think. And I love the idea of bringing the screening to patients where they are. I can speak to working in a regional healthcare system with a main campus in the downtown that patients absolutely hate having to come here from even 30 or 40 minutes away, and they'd much rather get their care locally. So that makes perfect sense.  So, under the current guidelines, there are certainly things that we can do to try to improve capturing the people that meet those. But are those guidelines actually capturing enough patients with lung cancer to make a difference? There certainly are proposals within patient advocacy communities and even other countries where there's a large percentage of non-smokers who perhaps get lung cancer. Can we expand beyond just older, current and heavy smokers to identify at-risk populations who could benefit from screening? Dr. Cheryl Czerlanis: Yes, I think we can, and it's certainly an active area of research interest. We know that tobacco is the leading cause of lung cancer worldwide. However, other risk factors include secondhand smoke, family history, exposure to environmental carcinogens, and pulmonary diseases like COPD and interstitial lung disease. Despite these known associations, the benefit of lung cancer screening is less well elucidated in never-smokers and those at risk of developing lung cancer because of family history or other risk factors. We know that the eligibility criteria associated with our current screening guidelines focus on age and smoking history and may miss more than 50% of lung cancers. Globally, 10% to 25% of lung cancer cases occur in never-smokers. And in certain parts of the world, like you mentioned, Nate, such as East Asia, many lung cancers are diagnosed in never-smokers, especially in women. Risk-prediction models use specific risk factors for lung cancer to enhance individual selection for screening, although they have historically focused on current or former smokers.  We know that individuals with family members affected by lung cancer have an increased risk of developing the disease. To this end, several large-scale, single-arm prospective studies in Asia have evaluated broadening screening criteria to never-smokers, with or without additional risk factors. One such study, the Taiwan Lung Cancer Screening in Never-Smoker Trial, was a multicenter prospective cohort study at 17 medical centers in Taiwan. The primary outcome of the TALENT trial was lung cancer detection rate. Eligible patients aged 55 to 75 had either never smoked or had a light and remote smoking history. In addition, inclusion required one or more of the following risk factors: family history of lung cancer, passive smoke exposure, history of TB or COPD, a high cooking index, which is a metric that quantifies exposure to cooking fumes, or a history of cooking without ventilation. Participants underwent low-dose CT screening at baseline, then annually for 2 years, and then every 2 years for up to 6 years. The lung cancer detection rate was 2.6%, which was higher than that reported in the NLST and NELSON trials, and most were stage 0 or I cancers. Subsequently, this led to the Taiwan Early Detection Program for Lung Cancer, a national screening program that was launched in 2022, targeting 2 screening populations: individuals with a heavy history of smoking and individuals with a family history of lung cancer.  We really need randomized controlled trials to determine the true rates of overdiagnosis or finding cancers that would not lead to morbidity or mortality in persons who are diagnosed, and to establish whether the high lung detection rates are associated with a decrease in lung cancer-related mortality in these populations. However, the implementation of randomized controlled low-dose CT screening trials in never-smokers has been limited by the need for large sample sizes, lengthy follow-up, and cost.  In another group potentially at higher risk for developing lung cancer, the role of lung cancer screening in individuals who harbor germline pathogenic variants associated with lung cancer also needs to be explored further. Dr. Nate Pennell: We had this discussion when the first criteria came out because there have always been risk-based calculators for lung cancer that certainly incorporate smoking but other factors as well and have discussion about whether we should be screening people based on their risk and not just based on discrete criteria such as smoking. But of course, the insurance coverage for screening, you have to fit the actual criteria, which is very constrained by age and smoking history. Do you think in the U.S. there's hope for broadening our screening beyond NLST and NELSON criteria? Dr. Cheryl Czerlanis: I do think at some point there is hope for broadening the criteria beyond smoking history and age, beyond the criteria that we have typically used and that is covered by insurance. I do think it will take some work to perhaps make the prediction models more precise or to really understand who can benefit. We certainly know that there are many patients who develop lung cancer without a history of smoking or without family history, and it would be great if we could diagnose more patients with lung cancer at an earlier stage. I think this will really count on there being some work towards trying to figure out what would be the best population for screening, what risk factors to look for, perhaps using some new technologies that may help us to predict who is at risk for developing lung cancer, and trying to increase the group that we study to try and find these early-stage lung cancers that can be cured. Dr. Nate Pennell: Part of the reason we, of course, try to enrich our population is screening works better when you have a higher pretest probability of actually having cancer. And part of that also is that our technology is not that great. You know, even in high-risk patients who have CT scans that are positive for a screen, we know that the vast majority of those patients with lung nodules actually don't have lung cancer. And so you have to follow them, you have to use various models to see, you know, what the risk, even in the setting of a positive screen, is of having lung cancer.  So, why don't we talk about some newer tools that we might use to help improve lung cancer screening? And one of the things that everyone is super excited about, of course, is artificial intelligence. Are there AI technologies that are helping out in early detection in lung cancer screening? Dr. Cheryl Czerlanis: Yes, that's a great question. We know that predicting who's at risk for lung cancer is challenging for the reasons that we talked about, knowing that there are many risk factors beyond smoking and age that are hard to quantify. Artificial intelligence is a tool that can help refine screening criteria and really expand screening access. Machine learning is a form of AI technology that is adept at recognizing patterns in large datasets and then applying the learning to new datasets. Several machine learning models have been developed for risk stratification and early detection of lung cancer on imaging, both with and without blood-based biomarkers. This type of technology is very promising and can serve as a tool that helps to select individuals for screening by predicting who is likely to develop lung cancer in the future.  A group at Massachusetts General Hospital, represented in our group for this paper by my co-authors, Drs. Fintelmann and Chang, developed Sybil, which is an open-access 3D convolutional neural network that predicts an individual's future risk of lung cancer based on the analysis of a single low-dose CT without the need for human annotation or other clinical inputs. Sybil and other machine learning models have tremendous potential for precision lung cancer screening, even, and perhaps especially, in settings where expert image interpretation is unavailable. They could support risk-adapted screening schedules, such as varying the frequency and interval of low-dose CT scans according to individual risk and potentially expand lung cancer screening eligibility beyond age and smoking history. Their group predicts that AI tools like Sybil will play a major role in decoding the complex landscape of lung cancer risk factors, enabling us to extend life-saving lung cancer screening to all who are at risk. Dr. Nate Pennell: I think that that would certainly be welcome. And as AI is working its way into pretty much every aspect of life, including medical care, I think it's certainly promising that it can improve on our existing technology.  We don't have to spend a lot of time on this because I know it's a little out of scope for what you covered in your paper, but I'm sure our listeners are curious about your thoughts on the use of other types of testing beyond CT screening for detecting lung cancer. I know that there are a number of investigational and even commercially available blood tests, for example, for detection of lung cancer, or even the so-called multi-cancer detection blood tests that are now being offered, although not necessarily being covered by insurance, for multiple types of cancer, but lung cancer being a common cancer is included in that. So, what do you think? Dr. Cheryl Czerlanis: Yes, like you mentioned, there are novel bioassays such as blood-based biomarker testing that evaluate for DNA, RNA, and circulating tumor cells that are both promising and under active investigation for lung cancer and multi-cancer detection. We know that such biomarker assays may be useful in both identifying lung cancers but also in identifying patients with a high-risk result who should undergo lung cancer screening by conventional methods. Dr. Nate Pennell: Anything that will improve on our rate of screening, I think, will be welcome. I think probably in the future, it will be some combination of better risk prediction and better interpretation of screening results, whether those be imaging or some combination of imaging and biomarkers, breath-based, blood-based. There's so much going on that it is pretty exciting, but we're still going to have to overcome the stigma and lack of public support for lung cancer screening if we're going to move the needle. Dr. Cheryl Czerlanis: Yes, I think moving the needle is so important because we know lung cancer is still a very morbid disease, and our ability to cure patients is not where we would like it to be. But I do believe there's hope. There are a lot of motivated individuals and groups who are passionate about lung cancer screening, like myself and my co-authors, and we're just happy to be able to share some ways that we can overcome the challenges and really try and make an impact in the lives of our patients. Dr. Nate Pennell: Well, thank you, Dr. Czerlanis, for joining me on the By the Book Podcast today and for all of your work to advance care for patients with lung cancer. Dr. Cheryl Czerlanis: Thank you, Dr. Pennell. It's such a pleasure to be with you today. Thank you. Dr. Nate Pennell: And thank you to our listeners for joining us today. You'll find a link to Dr. Czerlanis' article in the transcript of this episode.  Please join us again next month for By the Book's next episode and more insightful views on topics you'll be hearing at the education sessions from ASCO meetings throughout the year, and our deep dives on approaches that are shaping modern oncology. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:     Dr. Nathan Pennell    @n8pennell   @n8pennell.bsky.social Dr. Cheryl Czerlanis Follow ASCO on social media:     @ASCO on X (formerly Twitter)     ASCO on Bluesky    ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Nate Pennell:        Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron       Research Funding (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi    Dr. Cheryl Czerlanis: Research Funding (Institution): LungLife AI, AstraZeneca, Summit Therapeutics

Host Dr. Nate Pennell and his guest, Dr. Chloe Atreya, discuss the ASCO Educational Book article, “Integrative Oncology: Incorporating Evidence-Based Approaches to Patients With GI Cancers,” highlighting the use of mind-body approaches, exercise, nutrition, acupuncture/acupressure, and natural products. Transcript Dr. Nate Pennell: Welcome to ASCO Education: By the Book, our new monthly podcast series that will feature engaging discussions between editors and authors from the ASCO Educational Book. We'll be bringing you compelling insights on key topics featured in Education Sessions at ASCO meetings and some deep dives on the approaches shaping modern oncology.  I'm Dr. Nate Pennell, director of the Cleveland Clinic Lung Cancer Medical Oncology Program as well as vice chair of clinical research for the Taussig Cancer Institute. Today, I'm delighted to welcome Dr. Chloe Atreya, a professor of Medicine in the GI Oncology Group at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, and the UCSF Osher Center for Integrative Health, to discuss her article titled, “Integrative Oncology Incorporating Evidence-Based Approaches to Patients With GI Cancers”, which was recently published in the ASCO Educational Book. Our full disclosures are available in the transcript of this episode.  Dr. Atreya, it's great to have you on the podcast today. Thanks for joining me. Dr. Chloe Atreya: Thanks Dr. Pennell. It's a pleasure to be here. Dr. Nate Pennell: Dr. Atreya, you co-direct the UCSF Integrative Oncology Program with a goal to really help patients with cancer live as well as possible. And before we dive into the review article and guidelines, I'd love to just know a little bit about what inspired you to go into this field? Dr. Chloe Atreya: Yeah, thank you for asking. I've had a long-standing interest in different approaches to medicine from global traditions and I have a degree in pharmacology, and I continue to work on new drug therapies for patients with colorectal cancer. And one thing that I found is that developing new drugs is a long-term process and often we're not able to get the drugs to the patients in front of us. And so early on as a new faculty member at UCSF, I was trying to figure out what I could do for the patient in front of me if those new drug therapies may not be available in their lifetime. And one thing I recognized was that in some conversations the patient and their family members, even if the patient had metastatic disease, they were able to stay very present and to live well without being sidelined by what might happen in the future. And then in other encounters, people were so afraid of what might be happening in the future, or they may have regrets maybe about not getting that colonoscopy and that was eroding their ability to live well in the present.  So, I started asking the patients and family members who were able to stay present, “What's your secret? How do you do this?” And people would tell me, “It's my meditation practice,” or “It's my yoga practice.” And so, I became interested in this. And an entry point for me, and an entry point to the Osher Center at UCSF was that I took the Mindfulness-Based Stress Reduction Program to try to understand experientially the evidence for this and became very interested in it. I never thought I would be facilitating meditation for patients, but it became a growing interest. And as people are living longer with cancer and are being diagnosed at younger ages, often with young families, how one lives with cancer is becoming increasingly important.   Dr. Nate Pennell: I've always been very aware that it seemed like the patients that I treated who had the best quality of life during their life with cancer, however that ended up going, were those who were able to sort of compartmentalize it, where, when it was time to focus on discussing treatment or their scans, they were, you know, of course, had anxiety and other things that went along with that. But when they weren't in that, they were able to go back to their lives and kind of not think about cancer all the time. Whereas other people sort of adopt that as their identity almost is that they are living with cancer and that kind of consumes all of their time in between visits and really impacts how they're able to enjoy the rest of their lives. And so, I was really interested when I was reading your paper about how mindfulness seemed to be sort of like a formal way to help patients achieve that split. I'm really happy that we're able to talk about that. Dr. Chloe Atreya: Yeah, I think that's absolutely right. So, each of our patients is more than their cancer diagnosis. And the other thing I would say is that sometimes patients can use the cancer diagnosis to get to, “What is it that I really care about in life?” And that can actually heighten an experience of appreciation for the small things in life, appreciation for the people that they love, and that can have an impact beyond their lifetime. Dr. Nate Pennell: Just in general, I feel like integrative medicine has come a long way, especially over the last decade or so. So, there's now mature data supporting the incorporation of elements of integrative oncology into comprehensive cancer care. We've got collaborations with ASCO. They've published clinical practice guidelines around diet, around exercise, and around the use of cannabinoids. ASCO has worked with the Society for Integrative Oncology to address management of pain, anxiety, depression, fatigue – lots of different evidence bases now to try to help guide people, because this is certainly something our patients are incredibly interested in learning about. Can you get our listeners up to speed a little bit on the updated guidelines and resources supporting integrative oncology? Dr. Chloe Atreya: Sure. I can give a summary of some of the key findings. And these are rigorous guidelines that came together by consensus from expert panels. I had the honor of serving on the anxiety and depression panel. So, these panels will rate the quality of the evidence available to come up with a strength of recommendation. I think that people are at least superficially aware of the importance of diet and physical activity and that cannabis and cannabinoids have evidence of benefit for nausea and vomiting. They may not be aware of some of the evidence supporting these other modalities. So, for anxiety and depression, mindfulness-based interventions, which include meditation and meditative movement, have the strongest level of evidence. And the clinical practice guidelines indicate that they should be offered to any adult patient during or after treatment who is experiencing symptoms of anxiety or depression. Other modalities that can help with anxiety and depression include yoga and Tai Chi or Qigong. And with the fatigue guidelines, mindfulness-based interventions are also strongly recommended, along with exercise and cognitive behavioral therapy, Tai Chi and Qigong during treatment, yoga after treatment.  And some of these recommendations also will depend on where the evidence is. So, yoga is an example of an intervention that I think can be helpful during treatment, but most of our evidence is on patients who are post-treatment. So, most of our guidelines separate out during treatment and the post-treatment phase because the quality of evidence may be different for these different phases of treatment.  With the pain guidelines, the strongest recommendation is for acupuncture, specifically for people with breast cancer who may be experiencing joint pain related to aromatase inhibitors. However, acupuncture and other therapies, including massage, can be helpful with pain as well. So those are a few of the highlights. Dr. Nate Pennell: Yeah, I was surprised at the really good level of evidence for the mindfulness-based practices because I don't think that's the first thing that jumps to mind when I think about integrative oncology. I tend to think more about physical interventions like acupuncture or supplements or whatnot. So, I think this is really fantastic that we're highlighting this.  And a lot of these interventions like the Qigong, Tai Chi, yoga, is it the physical practice of those that benefits them or is it that it gives them something to focus on, to be mindful of? Is that the most important intervention? It doesn't really matter what you're doing as long as you have something that kind of takes you out of your experience and allows you to focus on the moment. Dr. Chloe Atreya: I do think it is a mind, body and spirit integration, so that all aspects are important. We also say that the best practice is the one that you actually practice. So, part of the reason that it's important to have these different modalities is that not everybody is going to take up meditation. And there may be people for whom stationary meditation, sitting and meditating, works well, and other people for whom meditative movement practices may be what they gravitate to. And so, I think that it's important to have a variety of options. And one thing that's distinct from some of our pharmacologic therapies is that the safety of these is, you know, quite good. So, it becomes less important to say, “Overall, is Tai Chi better or is yoga better?” for instance. It really depends on what it is that someone is going to take up. Dr. Nate Pennell: And of course, something that's been really nice evidence-based for a long time, even back when I was in my training in the 2000s with Jennifer Temel at Massachusetts General Hospital, was the impact of physical activity and exercise on patients with cancer. It seems like that is pretty much a universally good recommendation for patients. Dr. Chloe Atreya: Yes, that's absolutely right. Physical activity has been associated with improved survival after a cancer diagnosis. And that's both cancer specific survival and overall survival.  The other thing I'll say about physical activity, especially the mindful movement practices like Tai Chi and Qigong and yoga, is that they induce physiologic shifts in the body that can promote relaxation, so they can dampen that stress response in a physiologic way. And these movement practices are also the best way to reduce cancer-associated fatigue. Dr. Nate Pennell: One of the things that patients are always very curious about when they talk to me, and I never really feel like I'm as well qualified as I'd like to be to advise them around dietary changes in nutrition. And can you take me a little bit through some of the evidence base for what works and what doesn't work? Dr. Chloe Atreya: Sure. I do think that it needs to be tailored to the patient's needs. Overall, a diet that is plant-based and includes whole grains is really important. And I often tell patients to eat the rainbow because all of those different phytochemicals that cause the different colors in our fruits and vegetables are supporting different gut microbiota. So that is a basis for a healthy gut microbiome. That said, you know, if someone is experiencing symptoms related to cancer or cancer therapy, it is important to tailor dietary approaches. This is where some of the mindful eating practices can help. So, sometimes actually not just focusing on what we eat, but how we eat can help with symptoms that are associated with eating. So, some of our patients have loss of appetite, and shifting one's relationship to food can help with nutrition. Sometimes ‘slow it down' practices can help both with appetite and with digestion. Dr. Nate Pennell: One of the things that you said both in the paper and just now on our podcast, talking about how individualized and personalized this is. And I really liked the emphasis that you had on flexibility and self-compassion over rigid discipline and prescriptive recommendations here. And this is perhaps one of the real benefits of having an integrative oncology team that can work with patients as opposed to them just trying to find things online. Dr. Chloe Atreya: Yes, particularly during treatment, I think that's really important. And that was borne out by our early studies we called “Being Present.” So, after I was observing the benefits anecdotally among my patients of the ability to be present, we designed these pilot studies to teach meditation and meditative practices to patients. And in these pilot studies, the original ones were pretty prescriptive in a way that mindfulness-based stress reduction is fairly prescriptive in terms of like, “This is what we're asking you to do. Just stick with the program.” And there can be benefits if you can stick with the program. It's really hard though if someone is going through treatment and with GI cancers, it may be that they're getting chemotherapy every two weeks and they have one week where they're feeling really crummy and another week where they're trying to get things done. And we realized that sometimes people were getting overwhelmed and feeling like the mindfulness practice was another thing on their to-do list and that they were failing if they didn't do this thing that was important for them. And so, we've really kind of changed our emphasis. And part of our emphasis now is on incorporating mindfulness practices into daily life. Any activity that doesn't require a lot of executive function can be done mindfully, meaning with full attention. And so, especially for some of our very busy patients, that can be a way of, again, shifting how I'm doing things rather than adding a new thing to do. Dr. Nate Pennell: And then another part I know that patients are always very curious about that I'm really happy to see that we're starting to build an evidence base for is the use of supplements and natural products. So, can you take us a little bit through where we stand in terms of evidence behind, say, cannabis and some of the other available products out there? Dr. Chloe Atreya: Yeah, I would say that is an area that requires a lot more study. It's pretty complicated because unlike mindfulness practices where there are few interactions with other treatments, there is the potential for interactions, particularly with the supplements. And the quality of the supplements matters. And then there tends to be a lot of heterogeneity among the studies both in the patients and what other treatments they may be receiving, as well as the doses of the supplements that they're receiving.  One of my earliest mentors at Yale is someone named Dr. Tommy Chang, who has applied the same rigor that that we apply to testing of biomedical compounds to traditional Chinese medicine formulas. And so, ensuring that the formulation is stable and then formally testing these formulations along with chemotherapy. And we need more funding for that type of research in order to really elevate our knowledge of these natural products. We often will direct patients to the Memorial Sloan Kettering ‘About Herbs, Botanicals, and Other Products' database as one accessible source to learn more about the supplements. We also work with our pharmacists who can provide the data that exists, but we do need to take it with a grain of salt because of the heterogeneity in the data. And then it's really important if people are going to take supplements, for them to take supplements that are of high quality. And that's something in the article that we list all of the things that one should look for on the label of a supplement to ensure that it is what it's billed to be. Dr. Nate Pennell: So, most of what we've been talking about so far has really been applying to all patients with cancer, but you of course are a GI medical oncologist, and this is a publication in the Educational Book from the ASCO GI Symposium. GI cancers obviously have an incredibly high and rising incidence rate among people under 50, representing a quarter of all cancer incidence worldwide, a third of cancer related deaths worldwide. Is there something specific that GI oncologists and patients with GI cancers can take home from your paper or is this applicable to pretty much everyone? Dr. Chloe Atreya: Yeah, so the evidence that we review is specifically for GI cancers. So, it shows both its strengths and also some of the limitations. So many of the studies have focused on other cancers, especially breast cancer. In the integrative oncology field, there are definitely gaps in studying GI cancers. At the same time, I would say that GI cancers are very much linked to lifestyle in ways that are complicated, and we don't fully understand. However, the best ways that we can protect against development of GI cancers, acknowledging that no one is to blame for developing a GI cancer and no one is fully protected, but the best things that we can do for overall health and to prevent GI cancers are a diet that is plant-based, has whole grains. There's some data about fish that especially the deep-water fish, may be protective and then engaging in physical activity.  One thing I would like for people to take away is that these things that we know that are preventative against developing cancer are also important after development of a GI cancer. Most of the data comes from studies of patients with colorectal cancer and that again, both cancer specific and overall mortality is improved with better diet and with physical activity. So, this is even after a cancer diagnosis. And I also think that, and this is hard to really prove, but we're in a pretty inflammatory environment right now. So, the things that we can do to decrease stress, improve sleep, decrease inflammation in the body, and we do know that inflammation is a risk factor for developing GI cancers. So, I think that all of the integrative modalities are important both for prevention and after diagnosis. Dr. Nate Pennell: And one of the things you just mentioned is that most of the studies looking at integrative oncology and GI cancers have focused on colorectal cancer, which of course, is the most common GI cancer. But you also have pointed out that there are gaps in research and what's going on and what needs to be done in order to broaden some of this experience to other GI cancers. Dr. Chloe Atreya: Yeah, and I will say that there are gaps even for colorectal cancer. So right now, some of the authors on the article are collaborating on a textbook chapter for the Society for Integrative Oncology. And so, we're again examining the evidence specifically for colorectal cancer and are in agreement that the level of evidence specific to colorectal cancer is not as high as it is for all patients with adult cancers. And so even colorectal cancer we need to study more.  Just as there are different phases of cancer where treatments may need to be tailored, we also may need to tailor our treatments for different cancer types. And that includes what symptoms the patients are commonly experiencing and how intense the treatment is, and also the duration of treatment. Those are factors that can influence which modalities may be most important or most applicable to a given individual. Dr. Nate Pennell: So, a lot of this sounds fantastic. It sounds like things that a lot of patients would really appreciate working into their care. Your article focused a little bit on some of the logistics of providing this type of care, including group medical visits, multidisciplinary clinics staffed by multiple types of clinicians, including APPs and psychologists, and talked about the sustainability of this in terms of increasing the uptake of guideline-based integrative oncology. Talk a little bit more about both at your institution, I guess, and the overall health system and how this might be both sustainable and perhaps how we broaden this out to patients outside of places like UCSF. Dr. Chloe Atreya: Yes, that's a major focus of our research effort. A lot of comprehensive cancer centers and other places where patients are receiving care, people may have access to dietitians, which is really important and nutritionists. In the article we also provide resources for working with exercise therapists and those are people who may be working remotely and can help people, for instance, who may be in, in rural areas. And then our focus with the mind-body practices in particular has been on group medical visits. And this grew out of, again, my ‘being present' pilot studies where we were showing some benefit. But then when the grant ends, there isn't a way to continue to deliver this care. And so, we were asking ourselves, you know, is there a way to make this sustainable? And group medical visits have been used in other settings, and they've been working really well at our institution and other institutions are now taking them up as well. And this is a way that in this case it's me and many of my colleagues who are delivering these, where I can see eight or ten patients at once. In my case, it's a series of four two-hour sessions delivered by telehealth. So, we're able to focus on the integrative practices in a way that's experiential. So, in the clinic I may be able to mention, you know, after we go over the CT scans, after we go over the labs and the molecular profiling, you know, may be able to say, “Hey, you know, meditation may be helpful for your anxiety,” but in the group medical visits we can actually practice meditation, we can practice chair yoga. And that's where people have that experience in their bodies of these different modalities. And the feedback that we're receiving is that that sticks much more to experience it then you have resources to continue it. And then the group is helpful both in terms of delivery, so timely and efficient care for patients. It's also building community and reducing the social isolation that many of our patients undergoing treatment for cancer experience. Dr. Nate Pennell: I think that makes perfect sense, and I'm glad you brought up telehealth as an option. I don't know how many trained integrative oncologists there are out there, but I'm going to guess this is not a huge number out there. And much like other specialties that really can improve patients' quality of life, like palliative medicine, for example, not everyone has access to a trained expert in their cancer center, and things like telemedicine and telehealth can really potentially broaden that. How do you think telehealth could help broaden the exposure of cancer patients and even practitioners of oncology to integrative medicine? Dr. Chloe Atreya: Yes, I think that telehealth is crucial for all patients with cancer to be able to receive comprehensive cancer care, no matter where they're receiving their chemotherapy or other cancer-directed treatments. So, we will routinely be including patients who live outside of San Francisco. Most of our patients live outside of San Francisco. There's no way that they could participate if they had to drive into the city again to access this. And in the group setting, it's not even safe for people who are receiving chemotherapy to meet in a group most times. And with symptoms, often people aren't feeling so well and they're able to join us on Zoom in a way that they wouldn't be able to make the visit if it was in person. And so, this has really allowed us to expand our catchment area and to include patients, in our case, in all of California. You also mentioned training, and that's also important. So, as someone who's involved in the [UCSF] Osher Collaborative, there are faculty scholars who are at universities all over the US, so I've been able to start training some of those physicians to deliver group medical visits at their sites as well via telehealth. Dr. Nate Pennell: I'm glad we were able to make a plug for that. We need our political leadership to continue to support reimbursement for telehealth because it really does bring access to so many important elements of health care to patients who really struggle to travel to tertiary care centers. And their local cancer center can be quite a distance away.  So, sticking to the theme of training, clinician education and resources are really crucial to continue to support the uptake of integrative oncology in comprehensive cancer care. Where do you think things stand today in terms of clinician education and professional development in integrative oncology. Dr. Chloe Atreya: It's growing. Our medical students now are receiving training in integrative medicine, and making a plug for the Educational Book, I was really happy that ASCO let us have a table that's full of hyperlinks. So that's not typical for an article. Usually, you have to go to the reference list, but I really wanted to make it practical and accessible to people, both the resources that can be shared with patients that are curated and selected that we thought were of high-quality examples for patients. At the bottom of that table also are training resources for clinicians, and some of those include: The Center for Mind-Body Medicine, where people can receive training in how to teach these mind-body practices; The Integrated Center for Group Medical Visits, where people can learn how to develop their own group medical visits; of course, there's the Society for Integrative Oncology; and then I had just mentioned the Osher Collaborative Faculty Fellowship. Dr. Nate Pennell: Oh, that is fantastic. And just looking through, I mean, this article is really a fantastic resource both of the evidence base behind all of the elements that we've discussed today. Actually, the table that you mentioned with all of the direct hyperlinks to the resources is fantastic. Even recommendations for specific dietary changes after GI cancer diagnosis. So, I highly recommend everyone read the full paper after they have listened to the podcast today.  Before we wrap up, is there anything that we didn't get a chance to discuss that you wanted to make sure our listeners are aware of? Dr. Chloe Atreya: One thing that I did want to bring up is the disparities that exist in access to high quality symptom management care. So, patients who are racial and ethnic minorities, particularly our black and Latinx patients, the evidence shows that they aren't receiving the same degree of symptom management care as non-Hispanic White patients. And that is part of what may be leading to some of the disparities in cancer outcomes. So, if symptoms are poorly managed, it's harder for patients to stay with the treatment, and integrative oncology is one way to try to, especially with telehealth, this is a way to try to improve symptom management for all of our patients to help improve both their quality of life and their cancer outcomes. Dr. Nate Pennell: Well, Dr. Atreya, it's been great speaking with you today and thank you for joining me on the ASCO Education: By the Book Podcast and thank you for all of your work in advancing integrative oncology for GI cancers and beyond. Dr. Chloe Atreya: Thank you, Dr. Pennell. It's been a pleasure speaking with you. Dr. Nate Pennell: And thank you to all of our listeners who joined us today. You'll find a link to the article discussed today in the transcript of the episode. We hope you'll join us again for more insightful views on topics you'll be hearing at the Education Sessions from ASCO meetings throughout the year and our deep dives on approaches that are shaping modern oncology. Disclaimer: The purpose of this podcast is to educate, educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:    Dr. Nathan Pennell   @n8pennell  @n8pennell.bsky.social  Dr. Chloe Atreya  Follow ASCO on social media:    @ASCO on X (formerly Twitter)    ASCO on Bluesky   ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Nate Pennell:       Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron      Research Funding (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi   Dr. Chloe Atreya: Consulting or Advisory Role: Roche Genentech, Agenus Research Funding (Institution): Novartis, Merck, Bristol-Myers Squibb, Guardant Health, Gossamer Bio, Erasca, Inc.

On the inaugural episode of ASCO Education: By the Book, Dr. Nathan Pennell and Dr. Don Dizon share reflections on the evolution of the ASCO Educational Book, its global reach, and the role of its new companion podcast to further shine a spotlight on the issues shaping the future of modern oncology. TRANSCRIPT Dr. Nathan Pennell: Hello, I'm Dr. Nate Pennell, welcoming you to the first episode of our new podcast, ASCO Education: By the Book. The podcast will feature engaging discussions between editors and authors from the ASCO Educational Book. Each month, you'll hear nuanced views on key topics in oncology featured in Education Sessions at ASCO meetings, as well as some deep dives on the advances shaping modern oncology. Although I am honored to serve as the editor-in-chief (EIC) of the ASCO Educational Book, in my day job, I am the co-director of the Cleveland Clinic Lung Cancer Program and vice chair for clinical research for the Taussig Cancer Center here in Cleveland. I'm delighted to kick off our new podcast with a discussion featuring the Ed Book's previous editor-in-chief. Dr. Don Dizon is a professor of medicine and surgery at Brown University and works as a medical oncologist specializing in breast and pelvic malignancies at Lifespan Cancer Institute in Rhode Island. Dr. Dizon also serves as the vice chair for membership and accrual at the SWOG Cancer Research Network. Don, it's great to have you here for our first episode of ASCO Education: By the Book. Dr. Don Dizon: Really nice to be here and to see you again, my friend. Dr. Nathan Pennell: This was the first thing I thought of when we were kicking off a podcast that I thought we would set the stage for our hopefully many, many listeners to learn a little bit about what the Ed Book used to be like, how it has evolved over the last 14 years or so since we both started here and where it's going. You started as editor-in-chief in 2012, is that right? Dr. Don Dizon: Oh, boy. I believe that is correct, yes. I did two 5-year stints as EIC of the Educational Book, so that sounds about right. Although you're aging me very clearly on this podcast. Dr. Nathan Pennell: I had to go back in my emails to see if I could figure out when we started on this because we've been working on it for some time. Start out a little bit by telling me what do you remember about the Ed Book from back in the day when you were applying to be editor-in-chief and thinking about the Ed Book. What was it like at that time? Dr. Don Dizon: You know, it's so interesting to think about it.  Ten years ago, we were both in a very different place in our careers, and I remember when the Ed Book position came up, I had been writing a column for ASCO. I had done some editorial activities with other journals for sure, but what always struck me was it was very unclear how one was chosen to be a part of the education program at ASCO. And then it was very unclear how those faculty were then selected to write a paper for the Educational Book. And it was back in the day when the Educational Book was completely printed. So, there was this book that was cherished among American fellows in oncology. And it was one that, when I was newly attending, and certainly two or three years before the editor's position came up, it was one that I referenced all the time. So, it was a known commodity for many of us. And there was a certain sense of selectivity about who was invited to write in it. And it wasn't terribly transparent either. So, when the opportunity to apply for editor-in-chief of the Educational Book came up, I had already been doing so much work for ASCO. I had been on the planning committees and served in many roles across the organization, and editing was something I found I enjoyed in other work. So, I decided to put my name in the ring with the intention of sort of bringing the book forward, getting it indexed, for example, so that there was this credit that was more than just societal credit at ASCO. This ended up being something that was referenced and acknowledged as an important paper through PubMed indexing. And then also to provide it as a space where we could be more transparent about who was being invited and broadening the tent as to who could participate as an author in the Ed Book. Dr. Nathan Pennell: It's going to be surprising to many of our younger listeners to learn that the Educational Book used to be just this giant, almost like a brick. I mean, it was this huge tome of articles from the Education Sessions that you got when you got your meeting abstracts book at the annual meeting. And you can always see people on the plane on the way out of Chicago with their giant books. Dr. Don Dizon: Yes. Dr. Nathan Pennell: That added lots of additional weight to the plane, I'm sure, on the way out. Dr. Don Dizon: And it was not uncommon for us to be sitting at an airport, and people would be reading those books with highlighters. Dr. Nathan Pennell: I fondly remember being a fellow and coming up and the Ed Book was always really important to me, so I was excited. We'll also let the listeners in on that. I also applied to be the original editor-in-chief of the Ed Book back in 2012, although I was very junior and did not have any real editorial experience. I think I may have been section editor for The Oncologist at that point. And I had spoken to Dr. Ramaswamy Govindan at WashU who had been the previous editor-in-chief about applying and he was like, “Oh yeah. You should absolutely try that out.” And then when Dr. Dizon was chosen, I was like, “Oh, well. I guess I didn't get it.” And then out of the blue I got a call asking me to join as the associate editor, which I was really always very thankful for that opportunity. Dr. Don Dizon: Well, it was a highly fruitful collaboration, I think, between you and I when we first started. I do remember taking on the reins and sort of saying, “You know, this is our vision of what we want to do.” But then just working with the authors, which we did, about how to construct their papers and what we were looking for, all of that is something I look back really fondly on. Dr. Nathan Pennell: I think it was interesting too because neither one of us had really a lot of transparency into how things worked when we started. We kind of made it up a little bit as we went along. We wanted to get all of the faculty, or at least as many of them as possible contributing to these. And we would go to the ASCO Education Committee meeting and kind of talk about the Ed Book, and we were thinking about, you know, how could we get people to submit. So, at the time it wasn't PubMed indexed. Most people, I think, submitted individual manuscripts just from their talk, which could be anywhere from full length review articles to very brief manuscripts. Dr. Don Dizon: Sometimes it was their slides with like a couple of comments on it. Dr. Nathan Pennell: And some of them were almost like a summary of the talk. Yeah, exactly. And so sort of making that a little more uniform. There was originally an honorarium attached, which went away, but I think PubMed indexing was probably the biggest incentive for people to join. I remember that was one of the first things you really wanted to get. Dr. Don Dizon Yeah. And, you know, it was fortuitous. I'd like to take all the credit for it, but ASCO was very forward thinking with Dr. Ramaswamy and the conversations about going to PubMed with this had preceded my coming in. We knew what we needed to do to get this acknowledged, which was really strengthening the peer review so that these papers could meet the bar to get on PubMed. But you know, within the first, what, two or three years, Nate, of us doing this, we were able to get this accepted. And now it is. If you look at what PubMed did for us, it not only increased the potential of who was going to access it, but for, I think the oncology community, it allowed people access to papers by key opinion leaders that was not blocked by a paywall. And I thought that was just super important at the time. Social media was something, but it wasn't what it is now. But anybody could access these manuscripts and it's still the case today. Dr. Nathan Pennell: I think it's hard to overstate how important that was. People don't realize this, but the Ed Book is really widely accessed, especially outside the US as well. And a lot of people who can't attend the meeting to get the print, well, the once print, book could actually get access to essentially the education session from the annual meeting without having to fly all the way to the US to attend. Now, you know, we have much better virtual meeting offerings now and whatnot. But at the time it was pretty revolutionary to be able to do that. Dr. Don Dizon: Yeah, and you know, it's so interesting when I think back to, you know, this sort of evolution to a fully online publication of the Ed Book. It was really some requests from international participants of the annual meeting who really wanted to continue to see this in print. At that time, it was important to recognize that access to information was not uniform across the world. And people really wanted that print edition, maybe not for themselves, but so that access in more rural areas or where access in the broadband networks were not established that they still could access the book. I think things have changed now. We were able, I think, in your tenure, to see it fully go online. But even I just remember that being a concern as we went forward. Dr. Nathan Pennell: Yeah, we continued with the print book that was available if people asked for it, but apparently few enough people asked for it that it moved fully online. One of the major advantages of being fully online now is of course, it does allow us to publish kind of in real time as the manuscripts come out in the months leading up to the meeting, which has been, I think, a huge boon because it can build momentum for the Education Sessions coming in. People, you know, really look forward to it. Dr. Don Dizon: Yeah, that was actually a concern, you know, when we were phasing out Ed Book and going to this continuous publication model where authors actually had the ability to sort of revise their manuscript and that would be automatically uploaded. You had a static manuscript that was fully printed, and it was no longer an accurate one. And we did have the ability to fix it. And it just goes to show exactly what you're saying. This idea that these are living papers was really an important thing that ASCO embraced quite early, I think. Dr. Nathan Pennell: And with the onset of PubMed indexing, the participation from faculty skyrocketed and almost within a couple of years was up to the vast majority of sessions and faculty participating. Now I think people really understand that this is part of the whole process. But at the time I remember writing out on my slides in all caps, “THIS IS AN EXPECTATION.” And that's about the best word I could give because I asked if we could make people do it, and they were like, no, you can't make people do it. Dr. Don Dizon: So right.  Actually, I don't think people are aware of the work on the back end every year when I was on as EIC, Nate and myself, and then subsequently Dr. Hope Rugo would have these informational sessions with the education faculty and we would tout the Ed Book, tout the expectation, tout it was PubMed indexed and tout multidisciplinary participation. So, we were not seeing four manuscripts reflecting one session. You know, this encouragement to really embrace multidisciplinary care was something that very early on we introduced and really encouraged people not to submit perspective manuscripts, but to really get them in and then harmonize the paper so that it felt like it was, you know, one voice. Dr. Nathan Pennell: I consider that after PubMed indexing, the next major change to the Ed Book, that really made it a better product and that was moving from, you know, just these short individual single author manuscripts to single session combined manuscript that had multiple perspectives and topics, really much more comprehensive review articles. And I don't even remember what the impetus was for that, but it was really a success. Dr. Don Dizon: Yeah, I mean, I think in the beginning it was more of a challenge, I think, because people were really not given guidance on what these papers were supposed to look like. So, we were seeing individual manuscripts come forward. Looking back, it really foreshadowed the importance of multidisciplinary management. But at the time, it was really more about ensuring that people were leaving the session with a singular message of what to do when you're in clinic again. And the goal was to have the manuscripts reflect that sort of consensus view of a topic that was coming in. There were certain things that people still argued would not fit in a multidisciplinary manuscript. You know, if you have someone who's writing and whose entire talk was on the pathology of thyroid cancer. Another topic was on survivorship after thyroid cancer. It was hard to sort of get those two to interact and cover what was being covered. So, we were still getting that. But you're right, at the end of my tenure and into yours, there were far fewer of those individual manuscripts. Dr. Nathan Pennell: And I think it's even made it easier to write because now, you know, you just have to write a section of a manuscript and not put together an entire review. So, it has helped with getting people on board. Dr. Don Dizon: Well, the other thing I thought was really interesting about the process is when you're invited to do an Education Session at ASCO, you're either invited as a faculty speaker or as the chair of the session. And the responsibility of the chair is to ensure that it flows well and that the talks are succinct based on what the agenda or the objectives were as defined by the education committee for that specific group. But that was it. So really being named “Chair” was sort of an honor, an honorific. It really didn't come with responsibility. So, we use the Ed Book as a way to say, “As chair of the session, it is your responsibility to ensure A, a manuscript comes to me, but B, that the content of that paper harmonizes and is accurate.” And it was very rare, but Nate, I think we got dragged into a couple of times where the accuracy of the manuscript was really called into question by the chair. And those were always very, very tricky discussions because everyone that gets invited to ASCO is a recognized leader in their field. Some of us, especially, I would probably say, dating back 10 years from today, the data behind Standards of Care were not necessarily evidence-based. So, there were a lot of opinion-based therapies. You know, maybe not so much in the medical side, but certainly some of it. But when you went to, you know, surgical treatments and maybe even radiotherapy treatments, it was really based on, “My experience at my center is this and this is why I do what I do.” But those kinds of things ended up being some of the more challenging things to handle as an editor. Dr. Nathan Pennell: And those are the– I'll use “fun” in a broad sense. You know, every once in a while, you get an article where it really does take a lot of hands-on work from the editor to work with the author to try to revise it and make it a suitable academic manuscript. But you know what? I can't think, at least in recent years, of any manuscripts that we turned down. They just sometimes needed a little TLC. Dr. Don Dizon: Yeah. And I think the other important thing it reminds me of is how great it was that I wasn't doing this by myself. Because it was so great to be able to reach out to you and say, “Can you give me your take on this paper?” Or, “Can you help me just join a conference call with the authors to make sure that we're on the same page?” And then on the rare example where we were going to reject a paper, it was really important that we, as the editorial team, and I include our ASCO shepherder, through the whole process. We had to all agree that this was not salvageable. Fortunately, it happened very rarely. But I've got to say, not doing this job alone was one of the more important facets of being the EIC of ASCO's Educational Book. Dr. Nathan Pennell: Well, it's nice to hear you say that. I definitely felt that this was a partnership, you know, it was a labor of love. So, I want to go to what I consider sort of the third major pillar of the changes to the Ed Book during your tenure, and that was the introduction of a whole new kind of manuscript. So up to, I don't know, maybe seven or eight years ago, all the articles were authored just by people who were presenting at the Annual Meeting. And then you had an idea to introduce invited manuscripts. So take me through that. Dr. Don Dizon: Yeah, well, you know, again, it went to this sort of, what can people who are being asked to sort of lead ASCO for that year, what can they demonstrate as sort of a more tangible contribution to the Society and to oncology in general? And I think that was the impetus to use the Ed Book for everyone who was in a leadership position to make their mark. That said, I was here, and I was either president of the society or I was Education Program Chair or Scientific Program Chair, and they got to select an article type that was not being covered in the annual meeting and suggest the authors and work with those authors to construct a manuscript. Never did any one of those folks suggest themselves, which I thought was fascinating. They didn't say, “I want to be the one to write this piece,” because this was never meant to be a presidential speech or a commemorative speech or opportunity for them as leaders. But we wanted to ensure that whatever passion they had within oncology was represented in the book. And again, it was this sort of sense of, I want everyone to look at the Ed Book and see themselves in it and see what they contributed. And that was really important for those who were really shepherding each Annual Meeting each year for ASCO that they had the opportunity to do that. And I was really pleased that leadership really took to that idea and were very excited about bringing ideas and also author groups into the Educational Book who would not have had the opportunity otherwise. I thought that was just really nice. It was about inclusiveness and just making sure that people had the opportunity to say, “If you want to participate, we want you to participate.” Dr. Nathan Pennell: Yeah, I agree. I think the ASCO leadership jumped on this and continues to still really appreciate the opportunity to be able to kind of invite someone on a topic that's meaningful to them. I think we've tried to work in things that incorporate the presidential theme each year in our invited manuscript, so it really allows them to put kind of a stamp on the flavor of each edition. And the numbers reflect that these tend to be among our more highly read articles as well. Dr. Don Dizon: You know, looking back on what we did together, that was something I'm really, really quite proud of, that we were able to sort of help the Educational Book evolve that way. Dr. Nathan Pennell: I agree. You brought up briefly a few minutes ago about social media and its role over time. I think when we started in 2012, I had just joined Twitter now X in 2011, and I think we were both sort of early adopters in the social media. Do you feel like social media has had a role in the growth of the Ed Book or is this something that you think we can develop further? Dr. Don Dizon: When we were doing Ed Book together, professional social media was actually a quite identified space. You know, we were all on the same platform. We analyzed what the outcomes were on that platform and our communities gathered on that platform. So, it was a really good place to highlight what we were publishing, especially as we went to continuous publishing.  I don't remember if it was you or me, but we even started asking our authors for a tweet and those tweets needed work. It was you. It was you or I would actually lay in these tweets to say, “Yeah, we need to just, you know, work on this.” But I think it's harder today. There's no one preferred platform. Alternate platforms are still evolving. So, I think there are opportunities there. The question is: Is that opportunity meaningful enough for the Ed Book to demonstrate its return on an investment, for example? What I always thought about social media, and it's still true today, is that it will get eyes on whatever you're looking at far beyond who you intended to see it. So, you know, your tweets regarding a phase 3 clinical trial in lung cancer, which were so informative, were reaching me, who was not a lung oncologist who doesn't even see lung cancer and getting me more interested in finding that article and more and more pointing to the Educational Book content that speaks to that piece, you know. And I think coupling an impression of the data, associating that with something that is freely accessed is, I think, a golden opportunity not only for our colleagues, but also for anyone who's interested in a topic. Whether you are diagnosed with that cancer or you are taking care of someone with that cancer, or you heard about that cancer, there are people who would like to see information that is relevant and embedded and delivered by people who know what they're talking about. And I think our voices on social media are important because of it. And I think that's where the contribution is. So, if we had to see what the metric was for any social media efforts, it has to be more of the click rates, not just by ASCO members, but the click rates across societies and across countries. Dr. Nathan Pennell: Yeah, social media is, I mean, obviously evolving quite a bit in the last couple of years. But I do know that in terms the alt metrics for the track access through social media and online, the ones that are shared online by the authors, by the Ed Book team, do seem to get more attention. I think a lot of people don't like to just sit with a print journal anymore or an email table of contents for specific journals. People find these articles that are meaningful to them through their network and oftentimes that is online on social media. Dr. Don Dizon: Yes, 100%. And you know what I think we should encourage people to do is look at the source. And if the Ed Book becomes a source of information, I think that will be a plus to the conversations in our world. We're still dealing with a place where, depending on who sponsored the trial, whether it was an industry-sponsored trial, whether it was NCI sponsored or sponsored by the National Institutes of Health, for example, access to the primary data sets may or may not be available across the world, but the Ed Book is. And if the Ed Book can summarize that data and use terms and words that are accessible no matter what your grade level of education is. If we can explain the graphs and the figures in a way that people can actually easily more understand it. If there's a way that we structure our conversations in the Ed Book so that the plethora of inclusion/exclusion criteria are summarized and simplified, then I think we can achieve a place where good information becomes more accessible, and we can point to a summary of the source data in places where the source is not available. Dr. Nathan Pennell: One of the other things that I continue to be surprised at how popular these podcasts are. And that gives you an opportunity pretty much the opposite. Instead of sort of a nugget that directs you to the source material, you've got a more in-depth discussion of the manuscript. And so, I'm delighted that we have our own podcast. For many years, the Ed Book would sort of do a sort of a “Weird Al takeover” of the ASCO Daily News Podcast for a couple of episodes around the Annual Meeting, and I think those were always really popular enough that we were able to argue that we deserved our own podcast. And I'm really looking forward to having these in-depth discussions with authors. Dr. Don Dizon: It's an amazing evolution of where the Ed Book has gone, right? We took it from print only, societally only, to something that is now accessed worldwide via PubMed. We took it from book to fully online print. And now I think making the content live is a natural next step. So, I applaud you for doing the podcast and giving people an opportunity actually to discuss what their article discusses. And if there's a controversial point, giving them the freedom and the opportunity to sort of give more nuanced views on what may not be something that there's 100% consensus over. Dr. Nathan Pennell: Yes. Well, I hope other people enjoy these as well. Just want to highlight a few of the things that have happened just in the couple years since you stepped down as editor-in-chief. One of them, and I don't know if you noticed, but last year we started adding manuscripts from the ASCO thematic meetings, so ASCO GI and ASCO GU, something we had certainly talked about in the past, but had lacked bandwidth to really do. And they seem to be pretty widely accessed. Dr. Don Dizon: That's fantastic. Yes, I do remember talking about the coverage of the thematic meetings and you're right, this takes a long time to sort of concentrate on the Annual Meeting. It may seem like everything happens in the span of like eight weeks. Dr. Nathan Pennell: It does feel like that sometimes. Dr. Don Dizon: Right? But this is actually something that starts a year before, once the education program is set. We're in the room when they set it. But then it's really chasing down manuscripts and then making sure that they're peer reviewed because the peer review is still really important, and then making sure that any revisions are made before it's finalized and goes to press. That is a many months process. So, when we're trying to introduce, “Oh, we should also do ASCO GU or-,” the question was, how do you want to do that given this very, very involved process going forward? So, I'm glad you were able to figure it out. Dr. Nathan Pennell: Well, it's challenging. I don't think people realize quite the compressed timeline for these. You know, the Education Session and authors and invited faculty are picked in the fall, and then basically you have to start turning in your manuscripts in February, March of the following year. And so, it's a really tight turnaround for this. When we talk about the ASCO thematic meetings, it's an even tighter window. Dr. Don Dizon: Right, exactly. Dr. Nathan Pennell: And so, it's challenging to get that moving, but I was really, really proud that we were able to pull that off. Dr. Don Dizon: Well, congratulations again. And I think that is a necessary step, because so much of what's going on in the various disease management sites is only covered cursorily through the Annual Meeting itself. I mean, there's just so much science breaking at any one time that I think if we want to comprehensively catalog the Year in Review in oncology, it kind of behooves us to do that. Dr. Nathan Pennell: Some other things that are coming up because we now have manuscripts that are going to be coming in year-round, and just to kind of make it easier on the editorial staff, we're going to be forming an editorial board. And in addition to our pool of reviewers who get ASCO points, please feel free to go online to the ASCO volunteer portal and sign up if you are interested in participating. So, moving forward, I'm really excited to see where things are going to go. Dr. Don Dizon: Well, that's great. That's great. And I do remember talking about whether or not we needed to have an editorial board. At least when I was there, having this carried by three people was always better than having it carried by one person. And I think as you expand the potential for submissions, it will be very helpful to have that input for sure. And then it gives another opportunity for more members to get involved in ASCO as well. Dr. Nathan Pennell: Absolutely. People want involvement, and so happy to provide that. Dr. Don Dizon: Yes. Dr. Nathan Pennell: Is there anything we didn't cover that you would like to mention before we wrap up? Dr. Don Dizon: Well, I will say this, that ASCO and through its publications not only has had this real emphasis on multidisciplinary management of cancers, especially where it was relevant, but it also always had a stand to ensure representation was front and center and who wrote for us. And I think every president, every chair that I've worked with naturally embraced that idea of representation. And I think it has been a distinct honor to say that during my tenure as EIC, we have always had a plethora of voices, of authors from different countries, of genders, that have participated in the construction of those books. And it stands as a testament that we are a global community and we will always be one. Dr. Nathan Pennell: Well, thank you for that. And I'm happy to continue that as we move forward. Well, Don, thank you. It's been great speaking with you. You played such a pivotal role in the Ed Book's evolution and I'm so glad you were able to join me for our inaugural episode. Dr. Don Dizon: Well, I'm just tickled that you asked me to be your first guest. Thank you so much, Nate. Dr. Nathan Pennell: And I also want to thank our listeners for joining us today. We hope you'll join us again for more insightful views on topics you'll be hearing at the Education Sessions from ASCO meetings throughout the year, as well as our periodic deep dives on advances that are shaping modern oncology. Have a great day. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Nathan Pennell  @n8pennell @n8pennell.bsky.social   Dr. Don Dizon @drdondizon.bsky.social  Follow ASCO on social media:   @ASCO on X (formerly Twitter)   ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn   Disclosures:  Dr. Nathan Pennell:      Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron     Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  Dr. Don Dizon: Stock and Other Ownership Interests: Midi, Doximity Honoraria: UpToDate, American Cancer Society Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Kronos Bio, Immunogen Research Funding (Institution): Bristol-Myers Squibb          

Dr. Nathan Pennell and Dr. John Sweetenham discuss the evolving landscape of oncology in 2025 and the challenges oncologists will be facing, including the impact of Medicare drug price negotiations, ongoing drug shortages, and the promising role of AI and telehealth in improving patient outcomes and access to clinical trials. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. 2025 promises to be a year of continued progress in drug development, patient care, and technological innovations that will shape the future of cancer care. Oncologists will also be grappling with some familiar challenges in oncology practice and probably face a few new ones as well. I'm delighted to be joined today by Dr. Nathan Pennell to discuss some of these challenges. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research at the Taussig Cancer Center. He also serves as the editor-in-chief of the ASCO Educational Book.  You'll find our full disclosures in the transcript of this episode.  Nate, it's great to have you on the podcast today. Dr. Nathan Pennell: Thanks for inviting me, John. I'm excited to be here. Dr. John Sweetenham: Thanks. So, Nate, we've been hearing a lot recently about implementation science in oncology particularly. This has been the case, I would say, over the past decade and of course the goal is to how do we figure out the best way to integrate evidence-based practice into oncology care? There's been a lot of very good guidance from organizations like ASCO and every year we're reminded of the need for clinical decision support for practicing oncologists at the point of care. Although I think we all agree it is the right thing to do, and this has been a matter of discussion for probably more than 10 years, for the most part, I don't think we've really got there. Some big practices probably have a truly well-integrated clinical decision support tool, but for many of us this is still lacking in the field. I wonder whether we do need some kind of global clinical decision support tool. What do you think about the future of clinical decision support at the point of care? And do you think this is going to continue to be a need? Dr. Nathan Pennell: I think that's a fantastic question and it absolutely is something we're going to continue to work towards. We're in an incredibly exciting time in oncology. We've got all these exciting predictive biomarkers, effective treatments that are working better than anything we've had in our careers up to this point. But when we actually look to see who is benefiting from them, what we find is that outside of clinical trial populations, many of our patients aren't actually accessing these. And so publications that look at real-world use of these, one that jumps to mind for me is a publication looking at biomarker testing for driver oncogenes in lung cancer showed that while everyone who treats lung cancer says, “Absolutely, we need to test for biomarkers such as EGFR mutations,” in the real world, probably only slightly over a third of people ever access these drugs because there are so many different gaps in care that fall through the cracks. And so decision support is absolutely critical.  You mentioned this has been going on for a decade. Actually, the Institute of Medicine in 2013 recommended that with the uptake of electronic medical records, that we move forward with building these true learning health care systems that would improve quality and use every patient's information to help inform their care. And in 2023, as a representative of ASCO, I was able to look back at the last decade, and the uniform conclusion was that we had failed to build this learning health care system. So, what can we do going forward? The good news is there are improvements in technology. There are, for better or for worse, some consolidation of electronic medical records that has allowed larger numbers of patients to sort of have data sets shared. ASCO started CancerLinQ to try to improve quality, which is now part of OpenAI, and is still working on technology solutions to help provide decision support as we are better able to access patient data. And I think we're going to talk a little bit later about some of the technological advances that are going on in artificial intelligence that are really going to help improve this. So I think this is very close to impacting patient care and improving quality of care. I think for, as you'd mentioned, large health care systems and users of the major EMRs, this is going to be extremely close. Dr. John Sweetenham: Thanks, Nate. And just to extend the conversation into another area, one of the constant, I think, pain points for practicing oncologists has been the issue of prior authorization and the amount of time and energy it takes to deal with insurance denials in cancer care. And I think in a way, these two things are linked in as much as if we had clinical decision support tools at the point of care which were truly functional, then hopefully there would be a more facile way for an oncologist to be able to determine whether the patient in front of him or her is actually covered for the treatment that the oncologist wants to prescribe. But nevertheless, we're really not there yet, although, I think we're on the way to being there. But it does remain, like I said, a real pain point for oncologists.  I wonder if you have any thoughts on the issue of prior authorization and whether you see in the coming year anything which is going to help practicing oncologists to overcome the time and effort that they spend in this space. Dr. Nathan Pennell: I think many oncologists would have to list this among, if not the least favorite aspects of our job these days is dealing with insurance, dealing with prior authorizations. We understand that health care is incredibly expensive. We understand that oncology drugs and tests are even more expensive, probably among, if not the most rapidly growing costs to the health care system in the U.S., which is already at about 20% of our GDP every year. And so I understand the concern that costs are potentially unsustainable in the long term. Unfortunately, the major efforts to contain these costs seem to have fallen on the group that we would least like to be in charge of that, which are the payers and insurance companies, through use of prior authorization. And this is good in concept, utilization review, making sure that things are appropriate, not overutilizing our expensive treatments, that makes perfect sense. Unfortunately, it's moved beyond expensive treatments that have limited utility to more or less everything, no matter how inexpensive or standard. And there's now multiple publications suggesting that this is taking on massive amounts of time. Some even estimated that for each physician it's a full 40-hour work week per physician from someone to manage prior authorizations, which costs billions of dollars for practices every year. And so this is definitely a major pain point.  It is, however, an area where I'm kind of optimistic, maybe not necessarily in 2025, but in the coming several years with some of the technology solutions that are coming out, as we've talked about, with things like clinical pathways and whatnot, where the insurance company approvals can be tied directly to some of these guideline concordance pathway tools. So the recent publication at the ASCO Quality [Care] Symposium looking at a radiation oncology practice that had a guideline concordant prior auth tool that showed there was massive decrease in denials by using this. And as this gets rolled out more broadly, I think that this can increase the concept of gold carding, where if practices follow these clinical guidelines to a certain extent, they may be even exempt from prior authorization. I think I can envision that this is very close to potentially removing this as a major problem. I know that ASCO certainly has advocated on the national level for changes to this through, for example, advocating for the Improving Seniors Timely Access to Care Act. But I think, unfortunately, the recent election, I'm not sure how much progress will be made on the national level for progress in this. So I think that the market solutions with some of the technology interventions may be the best hope. Dr. John Sweetenham: Yeah, thanks. You raised a couple of other important points in that answer, Nate, which I'll pick up on now. You mentioned drug prices, and of course, during 2025, we're going to see Medicare negotiating drug prices. And we've already seen, I think, early effects from that. But I think it's going to be really interesting to see how this rolls out for our cancer patients in 2025. And of course, the thing that we can't really tell at the moment that you've alluded to is how all this is going to evolve with the new administration of President Trump. I understand, of course, that none of us really knows at this point; it's too early to know what the new administration will do. But would you care to comment on this in any way and about your concerns and hopes for Medicare specifically and what the administration will do to cancer care in general? Dr. Nathan Pennell: I think all of us are naturally a little bit anxious about what's going to happen under the new administration. The good news, if there's good news, is that under the first Trump administration, the National Cancer Institute and cancer care in general was pretty broadly supported both in Congress and by the administration. And if we look at specifically negotiating drug prices by Medicare, you can envision that having a businessman president who prides himself in negotiations might be something that would be supported and perhaps even expanded under the incoming Trump administration. So I think that's not too hard to imagine, although we don't really know. On the other hand, there are very valid concerns about what's going to happen with the Affordable Care Act, with Medicaid expansion, with protections for preexisting conditions, which impact our patients with cancer. And obviously there are potential people in the new administration who perhaps lack trust in traditional evidence-based medicine, vaccines, things like that, which we're not sure where they're going to fall in terms of the health care landscape, but certainly something we'll have to watch out for. Dr. John Sweetenham: Yeah. Certainly, when we regroup to record next year's podcast, we may have a clearer picture of how that's going to play out. Dr. Nathan Pennell: I mean, if there's anything good from this, it's that cancer has always been a bipartisan issue that people support. And so I don't want to be too negative about this. I do think that public support for cancer is likely to continue. And so overall, I think we'll probably be okay. Dr. John Sweetenham: Yeah, I agree with that. And I think one of the things that's important to remember, I do remember that one of the institutions I've worked at previously that there from time to time was some discussion about politics and cancer care. And the quote that I always remember is “We all belong to the cancer party,” and that's what's really important. So let's just keep our eye on the board. I hope that we can do that.  I'm going to switch gears just a little bit now because another issue which has been quite prominent in 2024 and in a few years before that has been supply chain issues and drug shortages. We've seen this over many years now, but obviously the problems have apparently been exacerbated in recent years, particularly by climate events. But certainly ASCO has published some recommendations in terms of quality care delivery for patients with cancer. Can you tell us a little bit about how you think this will go in the coming year and what we can do to address some of the concerns that are there over drug shortages? Dr. Nathan Pennell: Yeah. This continues to be, I think, a surprising issue for many oncologists because it has been going on for a long time, but really hasn't been in the public eye. The general problem is that once drugs go off patent and become generic, they often have limited manufacturers that are often outside the U.S. sometimes even a single manufacturer, which leaves them extremely vulnerable to supply chain disruption issues or regulatory issues. So situations where the FDA inspects and decides that they're not manufacturing things up to snuff and suddenly the only manufacturer is temporarily shut down. And then as you mentioned, things like extreme weather events where we had Hurricane Maria hit Puerto Rico and suddenly we have no bags of saline for several months. And so these are major issues which I think have benefited from being in the public eye.  ASCO, on the one hand, has, I think, done an excellent job leading on what to do in scenarios where there are shortages. But I think more importantly, we need more attention on a national level to policy changes that would help prevent this in the future. Some suggestions have been to increase some of the oversight of the FDA into supply chain issues and generic drugs, perhaps forming more of an early warning system to anticipate shortages so that we can find workarounds, find alternative suppliers that perhaps aren't currently being widely utilized. We can advocate for our legislators to pass legislation to support drug production for vital agents through things like long term contracts or even guaranteed pricing that might also even encourage U.S. manufacturers to take back up generic drugs if they were able to make it profitable. And then finally, I think just more of a national coordinated approach rather than the piecemeal approach we've done in the past. I remember when we had a platinum [drug] shortage last year. Our institution, with massive resources in our pharmacy, really did an excellent job of making sure that we always had enough supply. We never actually saw that shortage in real time, but I know a lot of places did not have those resources and therefore were really struggling. And so I think more of a coordinated approach with communication and awareness so that we can try to prevent this from happening. Dr. John Sweetenham: Thanks, Nate. And you raised the issue of major weather events, and I'd like to pick up on that for just a moment to talk about climate change. We now know that there is a growing body of evidence showing that climate change impacts cancer care. And it does it in a lot of ways. I mean, the most obvious is disrupting care delivery during one of these major events. But there are also issues about increased exposure to carcinogens, reduced access to food, reduced access to cancer screenings during these major disasters. And the recent hurricanes, of course, have highlighted the need for cancer centers to have robust disaster preparedness plans. In addition to that, obviously there are questions about greenhouse gas emissions and how cancer centers and health care organizations handle that.  But what do you see for 2025 in this regard? And what's your thinking about how well we're prepared as deliverers of cancer care to deal with these climate change issues? Dr. Nathan Pennell: Yeah, that is sobering to look at some of the things that have happened with climate change in recent years. I would love to say that I think that from a national level, we will see these changes and proactively work to reduce greenhouse emissions so that we can reduce these issues in the future. I'm not sure what we're going to see from the incoming administration and current government in terms of national policy on changes for fossil fuel use and climate change. I worry that there's a chance that we may see less done on the national level. I know the NCI certainly has policies in place to try to study climate change impact on cancer. It's possible that even that policy could be impacted by the incoming administration. So we'll have to see.  So, unfortunately, I worry that we may be still dealing in a reactive way to the impacts of this. So, obviously, wildfires causing carcinogens, pollution leading to increased cancer incidence, obviously, major weather events leading to physical disruptions, where cancer centers definitely have to have plans in place to help people maintain their treatment during those periods. As an individual, we can certainly make our impact on climate change. There are certainly organizations like Oncologists United for Climate and Health, or so-called OUCH, led by Dr. Joan Schiller, a friend of mine in the lung cancer world, where oncologists are advocating for policies to reduce use of fossil fuels. But I don't know, John, I don't know if I'm hopeful that there's going to be major policy changes on this in the coming year. Dr. John Sweetenham: I suspect you're right about that, although I think on the positive side, I think the issue as a whole is getting a lot more attention than it was maybe even two or three years ago. So that has to be a good thing that there's more advocacy and more attention out there now.  Nate, before we go on to the last question, because I do want to finish on a positive note, I just wanted to mention briefly that there are a couple of ongoing issues which, when we do this podcast each year, we normally address, and they certainly haven't gone away. But we know that burnout and workforce issues in oncology will continue to be a big challenge. The workforce issues may or may not be exacerbated by whatever the new administration's approach to immigration is going to be, because that could easily significantly affect the workforce in oncology. So that's one issue around workforce and burnout that we are not addressing in detail this year. But I wanted to raise it just because it certainly hasn't gone away and is going to continue to challenge us in 2025.  And then the other one, which I kind of put in the same category, is that of disparities. We continue to see ethnic and racial disparities of care. We continue to see disparities in rural areas. And I certainly wouldn't want to minimize the challenges that these are likely to continue to present in 2025. I wonder if you just have any brief comments you'd like to make and whether you think we're headed in the right direction with those issues. Dr. Nathan Pennell: Well, I'm somewhat optimistic in some ways about burnout. And I think when we get to our final topic, I think some of that may help. There may be some technology changes that may help reduce some of the influences of burnout. Disparities in care, obviously, I think similarly to some of the other issues we talked about have really benefited from just a lot of attention being cast on that. But again, I actually am optimistic that there are some technology changes that are going to help reduce some disparities in care. Dr. John Sweetenham: It's always great to finish one of these conversations on a positive note, and I think there is a lot to be very positive about. As you mentioned right at the beginning of the podcast, we continue to see quite extraordinary advances, remarkable advances in all fields of oncology in the therapeutic area, with just a massive expansion in not only our understanding, but also resulting from that improved understanding of the biology of the disease, the treatment advances that have come along. And so I think undoubtedly, we're going to see continued progress during 2025. And I know that there are technology solutions that you've mentioned already that you're very excited about. So, I'd really like to finish today by asking you if you could tell us a little about those and in particular what you're excited about for 2025. Dr. Nathan Pennell: Yeah. It's always dangerous to ask me to nerd out a little bit about some of these technology things, but I don't think that we can end any conversation about technology and not discuss the potential for artificial intelligence (AI) in health care and oncology. AI is sort of everywhere in the media and sort of already worked its way into our lives in our phones and apps that we're using and whatnot. But some of what I am seeing in tools that are probably going to be here very soon and, in some cases, already arriving, are pretty remarkable.  So some of the advances in natural language processing, or NLP, which in the past has been a barrier to really mining the vast amounts of patient information in the electronic medical record, is so much better now. So now, we can actually use technology to read doctor's notes, to read through scanned PDFs in our EMRs. And we can imagine that it's going to become very soon, much harder to miss abnormal labs, going to be much harder to miss findings on scans such as pulmonary nodules that get picked up incidentally. It's going to be much easier to keep up with new developments as clinical guidelines get worked in and decision support tools start reminding patients and physicians about evidence-based, high-quality recommendations. Being able to identify patients who are eligible for clinical trials is going to become much more easy.  And that leads me to the second thing, which is, throughout the pandemic we have greatly increased our use of telehealth, and this really has the potential to reduce disparities in care by reaching patients basically wherever they are. This is going to disproportionately allow us to access rural patients, patients that are currently underrepresented in clinical trials and whatnot, being able to present patients for clinical trials. In the recent “State of Cancer Care in America” report from ASCO, more than 60% of patients in the U.S. did not have access to clinical trials. And now we have the technology to screen them, identify them and reach out to and potentially enroll them in trials through use of decentralized elements for clinical trials. And so I'm very optimistic that not just good quality standard cancer care, but also clinical research is going to be greatly expanded with the use of AI and telehealth. Dr. John Sweetenham: Really encouraging to hear that. Nate, it's been a real pleasure speaking with you today and I want to thank you for taking the time to share your insights with us on the ASCO Daily News Podcast.  Dr. Nathan Pennell: Thanks, John. Dr. John Sweetenham: I also want to say thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Nathan Pennell @n8pennell   Dr. John Sweetenham   Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  

Dr. Nathan Pennell and Dr. Christopher Booth discuss Common Sense Oncology, a global initiative that aims to advance patient-centered, equitable care and improve access to treatments that provide meaningful outcomes. TRANSCRIPT Dr. Nate Pennell: Hello. I'm Dr. Nate Pennell, your guest host today for the ASCO Daily News Podcast. I'm the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research at the Taussig Cancer Center, and I also serve as the editor-in-chief of the ASCO Educational Book. My guest today is Dr. Christopher Booth, a professor of oncology and health sciences at Queen's University in Kingston, Ontario, where he also serves as the director of the Division of Cancer Care and Epidemiology. He joins me today to discuss his recently published article in the 2024 ASCO Educational Book titled, “Common Sense Oncology: Equity, Value, and Outcomes that Matter.” Dr. Booth also addressed this topic during a joint ASCO/European Cancer Organization session at the 2024 ASCO Annual Meeting.   Dr. Booth, welcome. Thanks for joining me. Dr. Christopher Booth: Thanks for inviting me here, and I look forward to our conversation. Dr. Nate Pennell: In your article in the Educational Book, and again, thank you so much to you and your co-authors for writing that for us, and during your presentation at the ASCO Annual Meeting, I think your topic really resonated with a lot of people. You explained that the essence of oncology is delivering compassionate care, and I really was struck by the statement, “the treatments need to provide meaningful care, meaningful improvements in outcomes that matter regardless of where the patients live.” Can you just tell us what exactly is Common Sense Oncology? What's your vision for what it can do to help address some of our growing challenges today?  Dr. Christopher Booth: Thanks, Nate. So, the Common Sense Oncology initiative was launched just over a year ago, and it really was a grassroots gathering of clinicians, policymakers, academics, as well as patients and patient advocates who recognize that there's many things we do well in the current cancer care system, but there's also areas that we can improve. And so it was created as a space for us to advocate for greater access for the things that we know really help people, but also to create a space where we can be willing to have some tough conversations and some humility and look within our field at some of the things that maybe aren't working as well as they should, and try to be constructive and not just be critics of the system, but actually be solution-focused and to try to move things forward. The Common Sense Oncology initiative, which has really taken off over the last year, really brings together people from all health systems who care deeply about people and their families who are with cancer. And our mission is that cancer care systems deliver treatments that have outcomes that matter to patients. And the vision is that, as you stated in your introduction, regardless of where someone lives, they have access to those cancer treatments which really do make a difference in their lives.  Dr. Nate Pennell: That certainly sounds like something everyone should be behind. Before we talk about some of what Common Sense Oncology may be doing to help address some of the inequities in cancer care, one of the challenges that is addressed in your paper is the focus on modern clinical trials and perhaps some of the mistakes that we're making in how they are designed. In many ways, we sort of live in a golden age of clinical trials with biomarker driven treatments, which can be incredibly effective in small populations of people, sometimes at great expense. So, focusing on our modern clinical trials, some of the criticisms that have arisen are that perhaps the endpoints that are being designed really aren't ones that are meaningful for patients, or that the gains that they're trying to look for in these trials may not be particularly meaningful. So, talk a little bit about that, if you might.  Dr. Christopher Booth One day, I might write a book called Paradoxes in Cancer Care. But there's a number of these things I think about. I'll start, Nate, in response to your question by talking about something I think of called the ‘three buckets paradox.' The three buckets paradox, I think, reflects a communication failure on the part of our field whereby if a patient or member of the public only reads the newspapers about cancer, they might wonder why we even have cancer hospitals and why Dr. Pennell and Dr. Booth even have a job, because everything we're doing is curing cancer. But we know the reality is different. And so, I conceptualize cancer treatments as going into three different buckets. We have the red bucket, which are those treatments, which really are transformational, and I've been working in oncology for 20 years now and we've seen a number of these treatments. They markedly increase cure rates or help people live for many, many months or extra years of life. And we have those treatments; they're almost out of a science fiction movie. The green bucket is a series of treatments. They're not perhaps transformational, but they're very, very good. They offer substantial benefits to our patients, and we have quite a few of those.  The concern that I think many of us recognize, and just to state emphatically that the problems that CSO is thinking about are not new problems; I think every oncologist has struggled with these things throughout each of our own careers. The concern is the third bucket, which includes many of our newer treatments, some of which, of course, are transformational. But many of the new treatments fall into this bucket, which have important side effects. They have major financial toxicity for patients' families and the system. They have time toxicity, especially in the last year of life. And the reality is most of these new treatments, either there's no proven benefit they help people live longer or better lives, or if they do, it's measured in a number of weeks. I think we need to reconcile the fact that we need to maybe speak honestly about some of the challenges in our field to recognize there's probably too many treatments going into that last bucket, and we need to push harder in the research ecosystem and the policy space to ensure we have more treatments in the first two buckets and that they remain widely available to everyone.  So, to get to the specific issues you raised in your question, Nate, some of the effect sizes and the endpoints we're choosing are problematic, I think. We have many, many examples of incredible clinical trials and new treatments that really make a difference for the lives of our patients. I want to state emphatically that the RCT remains the best tool we have to identify new treatments for patients of tomorrow, and any challenges with clinical trials, actually, it's not the fault of the RCT; these are self-inflicted by us who design, interpret, and act on clinical trials. And so the use of surrogate endpoints is a major issue in our field. And I just want to also state emphatically that there are circumstances where surrogate endpoints make a lot of sense and we should be using them. The problem is, I think with our excitement to get treatment answers more quickly, we've really embraced surrogate endpoints in a very, very rapid way. And in fact, I shouldn't even refer to them as surrogate endpoints. Maybe we should use the term alternative endpoints because in many cases they have been found to not be valid surrogates for those things which we know matter to patients: overall survival and quality of life. So certainly, there's a place for surrogate endpoints. I think we live in an era now where the majority of clinical trials are being designed to detect improvements in progression-free survival rather than overall survival. So historically, most clinical trials were being launched to see if we could help people live longer or feel better.  Now, the default endpoint is progression-free survival, which largely is based on tumor measurements on a CAT scan. And certainly, there are circumstances where those tumor measurements do relate to how someone feels or how long they live, but in most circumstances, that's not the case. I think we need to take a step back and just see the big picture here about where it is that we're going, and how can we raise the bar and ensure that we're identifying treatments that really offer meaningful gains to patients. Because we have to be honest about the fact that the patients and families are the ones who need to live through the side effects, the time toxicity and financial toxicity of these treatments. So, this is about maybe raising the bar and aiming a bit higher than we currently are.  Dr. Nate Pennell: And it looks like CSO basically is putting together teams around evidence generation, evidence interpretation and evidence communication that I guess, is trying to advocate and influence this? Dr. Christopher Booth: Yeah. So, when we launched this initiative, which now is this large global coalition of people, we wanted it to be really solution focused. So, our workstream is oriented around trying to improve how we generate evidence, how we interpret evidence, and how we communicate evidence. So, the evidence generation workstream is being led by a series of leading clinical trialists from all over the world, together with patients and patient advocates who are looking at how we can come up with a framework and principles to design, perhaps a more thoughtful approach to the design, reporting, and conduct of clinical trials. So that's kind of a clinical trials workstream. And I should mention all of these project teams are populated by clinicians, academics, members of the public, as well as patient and patient advocates who, in some cases, are co-leaders of the workstreams.  The evidence interpretation workstream is an educational bucket being led by clinicians and educators, together with patients, to see how we can improve the skill set of the next generation of oncologists to be better equipped in skills and epidemiology, critical appraisal, and critical thinking, so we can better dissect trials which have been well designed from those which might have some limitations, identify those treatments which have very substantial gains from those which are perhaps more marginal. And then the third workstream relates to how we communicate evidence. And this is communication broadly, how we talk about these very complex and nuanced issues at the bedside between oncologist and patient. But how we talk more broadly in society, through the media, with public and policy makers, about some of the challenges in cancer care, recognizing, of course, that no one individual, group or person is going to have the answer for what treatments matter for any specific patient. This is going to vary by every patient with their unique values, preferences and goals in life. But we think we can do a better job of talking about these issues and empowering patients to have the information they need so they can make the treatments that match their own goals and wishes.  Dr. Nate Pennell: Oh, thank you. Another thing that I was interested in in your paper, and when we talk about value and whether these endpoints that are being released for drugs that become approved are meaningful to patients, the other aspect of value is, of course, the cost. And we know that basically every new drug that gets approved, just an astronomical cost these days, which doesn't often factor into whether to approve them. It doesn't often factor into a doctor's decision about whether to use them. Can you talk a little bit about this? And is cost of drugs something that CSO is interested in addressing, or is that more of just a part of the equation in determining value of these? Dr. Christopher Booth: No, I think it's a really important point. So the value construct, I'm not an economist, so I think about this as a simple Canadian chemotherapy doctor would, which is the interface of what you get - so the magnitude of benefits, that's the endpoint, and the effect size - relative to the downsides, the cost, the clinical toxicity, time toxicity, and financial toxicity. So historically, I mean, I think, Nate, you and I will remember maybe 10 or 15 years ago when this really came on the scene, all the conversations focused on the denominator, the cost of cancer medicines, which became astronomical over the last 10 or 20 years. And we've learned a few things about that over time, and I'll get to that in a moment in reference to your question. But I think as individual clinicians or investigators, or even people writing guidelines, we don't have a lot of ability to influence the price of cancer medicines, although I think we still need to speak out about these prices, which are largely unjustified. I'll come back to that. But where I think there's growing interest, and we've seen this in the last five years, is the numerator in that value construct, which is the magnitude of benefit, the endpoint, the effect size. And I think that's where we actually have much more ability to influence. We are the doctors who make treatment recommendations, the experts who write guidelines, the investigators who design trials and so I think we need to take a bit more ownership when it comes to this magnitude of benefit construct. And that's where a lot of the work that Common Sense Oncology is doing rests.  But to answer your question about cost, this is a major problem. We've known that it's been shown by several groups that the price of a cancer medicine is not justified by the R and D cost, that's been shown over time. We also have a problem where the magnitude of benefit offered by that drug also has no bearing to the price. And so this speaks to the need to really, I think, undertake more rigorous health technology assessment and think very carefully about- you know every other economic model that you and I live in, Nate, if, you know, if we have a growing family, we need a larger apartment or house, we spend more money, we get a bigger house. If we want to keep up with our kids on their fast bicycles, we spend more money, we get a better bicycle. And when it comes to cancer medicines, we found that not only is there no relationship between how well the drug works and its price, our group and others have found, if anything, there's an inverse relationship, whereby the drugs with the smallest benefit have the largest price tag. And I don't think you need a PhD in economics to know that is an incredibly broken system. So, I think there's a lot that we need to talk about when it comes to cost. Common Sense Oncology cares deeply about this because it's a huge issue about health justice and global equity and access to cancer medicines. And I think we need to work on that. But we also can't forget about the numerator, which is, to what extent do these treatments help people? Dr. Nate Pennell: I know that every time I see one of these fabulous new presentations at ASCO Plenary or something like that, I just imagine many of the doctors and patients who live outside the U.S., maybe in low- and middle-income countries, who don't have the same access to basic oncology care and specialty oncology care that we do in Western countries, and what goes through their minds when they think about this. And so, I know that this is another big part of what CSO is doing, is thinking about global equity and access to cancer care. And so, can you tell me a little bit about how you're hoping to address that? Dr. Christopher Booth: Yeah. And so, you're right. I guess I'll tell you another Booth cancer paradox. I call this the cancer medicine paradox, which is, on the one hand, in many health systems, I think we'll recognize that there's often overutilization of cancer medicines that are toxic, expensive, and small benefits, especially in the last year of life. So, we have that kind of overutilization paradigm in some parts of the world, but we also have this paradox where we have massive underutilization of those treatments that we know actually have large benefits. And the tragic part of this is many of those treatments are old, generic drugs that actually should be very affordable. Some of this work comes out of myself and a number of my founding colleagues of Common Sense Oncology have a policy role with the World Health Organization Essential Medicine list. My interest in this started, I guess, many years ago when I had a sabbatical in India and lived and worked at a large government cancer hospital for a period of time. And so, from this WHO working group, we launched a project. It's been called the Desert Island study. It was called the Desert Island Project for reasons I'll tell you in a moment. But essentially it was a survey of 1,000 oncologists on the frontlines of care in 82 countries worldwide. And what we are interested in doing is in our role as an advisory group to the WHO Essential Medicine List, we come up with a list of those medicines which are really most important and should be provided in all health systems. And we were interested in going to the frontlines of care, leaving the boardroom of Geneva, and going to the frontlines of care and asking real doctors in the real world, “What medicines do you think are the most important for the patients that you look after?”   So, it was a survey. We asked a lot of demographic questions about their clinical practice and their health system, but we called it the Desert Island Project, because the core question of the survey was based on the thought experiment that you and I have done many times with friends at dinner parties. For example, if you're moving to a desert island and you could only take three books, what would those books be? If you're going to have dinner with any famous podcast host in the world other than Dr. Pennell, who would that person be? And so the thought experiment was, imagine your government has put you in charge of cancer care for your country. You can choose any cancer medicines you want that will be freely available for all cancers and all people in your country. Cost is not an issue, but you can only choose 10. You can only choose 10 of those medicines to take to the desert island to look after all the people in your country, what would those medicines be? And it's amazing; of those thousand oncologists, we found, first of all, remarkable convergence between doctors, regardless of where they work, whether it was a high-income country, middle-income country, lower-income country, the doctors were very pragmatic. When we looked at the drugs that went in that suitcase over and over again, the most common drugs were the good old fashioned cytotoxic chemotherapy drugs and hormone drugs we've been using for 20 or 30 years that we know have very, very large benefits, and in the modern era now should be very affordable because they've been off patent for many years.   In that list of medicines that went to the desert island, there also were some of our newer drugs that are new and they're very expensive. But they are those drugs that have very large benefits. And, of course, all of us would want access to those for our patients. So we found that the doctors are pretty pragmatic about which medicines if they're pushed to offer the largest benefit. But the next part of the question was, okay, you've told us which medicines you want to put in your suitcase to take to the desert island, please now tell us the reality in your health system to what extent can you deliver these medicines? And it was shocking. The vast majority of oncologists, a huge number of them, said they could not even provide doxorubicin or cisplatin without causing major financial toxicity for that patient and family. Even for trastuzumab, now available as a biosimilar, only 15% of oncologists globally said they could provide it universally to all women with breast cancer. Two thirds of oncologists said, “Look, I can give it, but I will catastrophically ruin that patient's family's finances for generations to come.” So, we have a big problem in the sense that we need to focus on those treatments which make a big difference and ensure that they're available to all patients who could benefit, while at the same time raise the bar so that the modern treatments that we're offering also have large benefits.  Dr. Nate Pennell: I think that's really eye opening, and I hope lots of people take away from this, that this is the reality for a huge number, potentially billions of people on the planet that don't have easy access to the same kinds of drugs. We're not even necessarily talking about the expensive drugs with the three-week DFS benefit, but ones that actually could be curing them of their breast cancer and their testicular cancer and their lymphomas, and they can't even get access to those, even though here we might say that they're inexpensive and relatively accessible. So how do we fix that? Maybe this is too big a question for a few minutes in a podcast, but I'm curious to see what CSO is doing to try to help.  Dr. Christopher Booth: Well, the challenges are substantial, and so that's why we've kind of created this group, because it's going to require kind of collective input, I think, of everyone in our field and beyond. And I also think, one of the reasons we've been overwhelmed with interest by the next generation, the young, the trainees, the young oncologists who are very interested in this, and I think they're recognizing that this might be an alternative place for them to put their energy, talent, as they build their own academic careers, is tackling some of these really, really tricky problems where the solutions are not immediately obvious. One thing I think, Nate, that's important is for us to talk about these things and recognize that there's a range of cancer treatments, and that this might help set better expectations for the patients and families when they walk into our cancer centers, let alone in the U.S. and Canada, but also globally. We've seen challenges with all of us as human beings are technophiles, we're drawn towards the new shiny targeted therapy or a robot or treatment in cancer care, and we've seen that play out somewhat tragically. Some of my friends and colleagues in LMICs have told stories where the Minister of Health is about to make a major investment in cancer care, but they want the shiny new monoclonal antibody, because that's perceived as being newer and better, when the reality is that that might add two months of PFS compared to other agents that are much, much- have much larger benefits and, of course, are much more affordable. And there's modeling where even just one of these new medicines, for one cancer, would wipe out the entire cancer medicine budget for that country. Yet we don't have tamoxifen, doxorubicin, cisplatin or even morphine for palliative care available. So, some of this is about socializing these issues, talking about these things that, again, these are not new problems. I think every oncologist worldwide has wrestled with these things, but just at least creating a space where we can talk honestly about this and work towards solutions.  Dr. Nate Pennell: Yeah, I think even just having the framework and the awareness and getting people involved is going to make a big difference. And of course, the people who ultimately are impacted the most by this are the patients with cancer. One of the big aspects in your paper is talking about how patients and patient advocates are central to the CSO movement. So, tell me a little bit about how they became involved and what role they play in CSO. Dr. Christopher Booth: Yeah, so this has been a very intentional and deliberate part of the building of the Common Sense Oncology initiative. So this started with a planning meeting of- a very small planning meeting of 30 people in Kingston, here at Queen's University just over a year ago, with 30 people from 15 different countries, a mix of academics, clinicians, editors, and in that room were five or six patients and patient advocates from day 1, because we wanted to make sure that this is really all about their needs and creating a system that revolves around the outcomes that matter to patients and families. So since then, we've continued to engage broadly. We have a patient priorities project team. There's co-leadership there. One is a colleague and oncologist from New Zealand, but the other co-leader is a patient advocate from- a breast cancer patient advocate from the United States. And all of our project teams have patients and patient advocates as part of their membership. The Patient Priorities Team is working to design a patient charter to guide the design and implementation of clinical trials from the patient's perspective. And as part of that exercise we've been undertaking, we call the CSO speaking and listening tour, where we've had a series of webinars with patient advocacy groups from all over the world, where part of the webinar is us talking about the CSO mission vision, workstream and some of the challenges and solutions we see so that we can provide some education, but also get honest feedback from the front lines to learn kind of where we might be off, what we might be missing, what we should focus on. But then also, the second part of the webinar is about sharing this kind of draft patient charter and getting more broad input from patients and families about what it is they're looking for in a cancer system. And I can tell you that some of the most gratifying correspondence I've had since launching CSO, which has been essentially become my third full time job, is letters from patients and family members of former patients who have since deceased or active patients on treatment, who are saying how much they appreciate this work and how much they feel that oncology can perhaps do a better job talking about some of these things. And they've been giving us some very good ideas and suggestions that, in fact, I'm already incorporating into my clinical practice, because ultimately all of us came into this field to help people with cancer, and I think they can and should and are remaining the center of everything. Dr. Nate Pennell: I think, thankfully, that is a movement throughout medicine, certainly cancer medicine, that patients are becoming more involved much earlier in the process of designing trials. And hopefully that alone will help change the endpoints that we're building into these studies to make them much more meaningful.   So, people are going to read your paper, they're going to get excited, they're going to listen to this podcast, they're going to get even more excited about how they're going to change the world through a little more common sense. So how can they get involved? Is this something that you're open to people working with you? Are there other things people can do to try to help solve some of these frustrating problems?  Dr. Christopher Booth: Yeah, absolutely, Nate. So, we have a website at commonsenseoncology.org. Some of our co-leaders are very active on social media, so they can follow us through social media channels. If you go to our website, there is a membership button where people can join. There's no fee and we won't bombard you with too many emails. But what that has allowed us to do is build this network of people who have diverse interests and skill sets that we can then tap into various projects and workstreams where we could use the help and support. And members have access to things like virtual webinars, journal clubs, critical appraisal sessions, and they get a newsletter from us every two or three months about activities and about ideas and allow exchange of dialogue going back and forth. So certainly, we look forward to growing this initiative, and the challenges are large, but we think that with the collective input of stakeholders from around the world, we could make a difference in moving towards some solutions. Dr. Nate Pennell: And for our listeners, that is commonsenseoncology.org. You can go check this out and join if you are interested in learning more.  Chris, thanks so much for sharing your insights and for all of your work on addressing these complex challenges in cancer care. Dr. Christopher Booth: Thanks, Nate. Grateful for the interview and also for ASCO for giving us the opportunity in the Educational Book and at the Annual Meeting to talk about this work. Dr. Nate Pennell: Thank you. And I also want to thank our listeners for joining us today. You'll find links to the article discussed today, as well as Dr. Booth's presentation at the Annual Meeting, in the transcript of the episode. Finally, if you value the insights that you heard on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Nathan Pennell @n8pennell Dr. Christopher Booth   Follow ASCO on social media:    @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Nathan Pennell: Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi    Dr. Christopher Booth: No relationships to disclose

Drs. Vamsi Velcheti and Nathan Pennell discuss novel approaches and key studies in lung cancer that were showcased at the 2024 ASCO Annual Meeting, including the Plenary abstracts LAURA and ADRIATIC.   TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. Today, I'm joined by Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and the vice chair of clinical research at the Taussig Cancer Center in Cleveland Clinic. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Today, we will be discussing practice-changing abstracts and the exciting advances in lung cancer that were featured at the ASCO 2024 Annual Meeting. You'll find our full disclosures in the transcript of the episode. Nate, we're delighted to have you back on the podcast today. Thanks for being here. It was an exciting Annual Meeting with a lot of important updates in lung cancer. Dr. Nate Pennell: Thanks, Vamsi. I'm glad to be back. And yes, it was a huge year for lung. So I'm glad that we got a chance to discuss all of these late-breaking abstracts that we didn't get to talk about during the prelim podcast. Dr. Vamsi Velcheti: Let's dive in. Nate, it was wonderful to see all the exciting data, and one of the abstracts in the Plenary Session caught my attention, LBA3. In this study, the investigators did a comparative large-scale effectiveness trial of early palliative care delivered via telehealth versus in-person among patients with advanced non-small cell lung cancer. And the study is very promising. Could you tell us a little bit more about the study and your take-home messages? Dr. Nate Pennell: Yes, I think this was a very important study. So just to put things in perspective, it's now been more than a decade since Dr. Jennifer Temel and her group at Massachusetts General Hospital did a randomized study that showed that early interventions with palliative medicine consultation in patients with advanced non-small cell lung cancer significantly improves quality of life and in her initial study, perhaps even overall survival. And since then, there have been numerous studies that have basically reproduced this effect, showing that getting palliative medicine involved in people with advanced cancer, multiple different cancer types, really, has benefits.  The difficulty in applying this has been that palliative care-trained specialists are few and far between, and many people simply don't have easy access to palliative medicine-trained physicians and providers. So with that in mind, Dr. Temel and her group designed a randomized study called the REACH PC trial, where 1,250 patients were randomized with advanced non-small cell lung cancer to either in-person palliative medicine visits which is sort of the standard, or one in-person assessment followed by monthly telemedicine video visits with palliative medicine. Primary endpoint was essentially to show that it was equivalent in terms of quality of life and patient satisfaction. And what was exciting about this was that it absolutely was. I mean, pretty much across the board in all the metrics that were measured, the quality-of-life, the patient satisfaction, the anxiety and depression scores, all were equivalent between doing telemedicine visits and in-person visits. And this hopefully will now extend the ability to get this kind of benefit to a much larger group of people who don't have to geographically be located near a palliative medicine program. Dr. Vamsi Velcheti: Yeah, I think it's a great abstract, Nate and I actually was very impressed by the ASCO committee for selecting this for the Plenary. We typically don't see supportive care studies highlighted in such a way at ASCO. This really highlights the need for true interdisciplinary care for our patients. And as you said, this study will clearly address that unmet need in terms of providing access to palliative care for a lot of patients who otherwise wouldn't have access. I'm really glad to see those results. Dr. Nate Pennell: It was. And that really went along with Dr. Schuchter's theme this year of bringing care to patients incorporating supportive care. So I agree with you.  Now, moving to some of the other exciting abstracts in the Plenary Session. So we were talking about how this was a big year for lung cancer. There were actually 3 lung cancer studies in the Plenary Session at the Annual Meeting. And let's move on to the second one, LBA4, the LAURA study. This was the first phase 3 study to assess osimertinib, an EGFR tyrosine kinase inhibitor, in patients with EGFR mutant, unresectable stage III non-small cell lung cancer. What are your takeaways from this study?  Dr. Vamsi Velcheti: This is certainly an exciting study, and all of us in the lung community have been kind of eagerly awaiting the results of the study. As you know, for stage III non-small cell lung cancer patients who are unresectable, the standard of care has been really established by the PACIFIC study with the consolidation durvalumab after definitive concurrent chemoradiation. The problem with that study is it doesn't really answer the question of the role of immunotherapy in patients who are never-smokers, and especially in patients who are EGFR positive tumors, where the role of immunotherapy in a metastatic setting has always been questioned. And in fact, there have been several studies as you know, in patients with EGFR mutation positive metastatic lung cancer where immunotherapy has not been that effective. In fact, in the subgroup analysis in the PACIFIC study, patients with EGFR mutation did not really benefit from adding immunotherapy.  So this is an interesting study where they looked at patients with locally advanced, unresectable stage III patients and they randomized the patients 2:1 to osimertinib versus placebo following concurrent or sequential tumor radiation. The primary endpoint for the study was progression free survival, and a total of 216 patients were enrolled and 143 patients received a study treatment, which is osimertinib, and 73 received placebo. And 80% of the patients on the placebo arm crossed over to getting treatment at the time of progression.  So most of us in the lung cancer community were kind of suspecting this would be a positive trial for PFS. But however, I think the magnitude of the difference was truly remarkable. The median PFS in the osimertinib arm was 39.1 months and placebo was 5.6 months and the hazard ratio of 0.16. So it was a pretty striking difference in terms of DFS benefit with the osimertinib consolidation following chemoradiation. So it was truly a positive study for the primary endpoint and the benefit was seen across all the subgroups and the safety was no unexpected safety signals other than a slight increase in the radiation pneumonitis rates in patients receiving osimertinib and other GI and skin tox were kind of as expected. In my opinion, it's truly practice changing and I think patients with EGFR mutation should not be getting immunotherapy consolidation post chemoradiation. Dr. Nate Pennell: I completely agree with you. I think that this really just continues the understanding of the use of osimertinib in EGFR-mutant lung cancer in earlier stages of disease. We know from the ADAURA trial, presented twice in the Plenary at the ASCO Annual Meeting, that for IB, stage II and resectable IIIA, that you prolong progression free or disease free survival. So this is a very similar, comparable situation, but at an even higher risk population or the unresectable stage III patients. I think that the most discussion about this was the fact that the osimertinib is indefinite and that it is distinct from the adjuvant setting where it's being given for three years and then stopped. But I think all of us had some pause when we saw that after three years, especially in the stage III patients from ADAURA, that there were clearly an increase in recurrences after stopping the drug, suggesting that there are patients who are not cured with a time limited treatment, or at least with 3 years of treatment.  The other thing that is sobering from the study, and was pointed out by the discussant, Dr. Lecia Sequist, is if you look at the two-year disease-free survival in the placebo arm, it was only 13%, meaning almost no one was really cured with chemo radiation alone. And that really suggests that this is not that different from a very early stage IV population where indefinite treatment really is the standard of care. I wonder whether you think that's a reasonable approach. Dr. Vamsi Velcheti: I completely agree with you, Nate, and I don't think we cure a majority of our patients with stage III, and less so in patients who have EGFR-mutant, stage III locally advanced. As you just pointed out, I think very few patients actually make it that far along. And I think there's a very high rate of CNS micrometastatic disease or just systemic micrometastatic disease in this population that an effective systemic therapy of osimertinib can potentially have long term outcomes. But again, we perhaps don't cure a vast majority of them. I think that the next wave of studies should incorporate ctDNA and MRD-based assays to potentially identify those patients who could potentially go off osimertinib at some point. But, again, outside of a trial, I would not be doing that. But I think it's definitely an important question to ask to identify de-escalation strategies with osimertinib. And even immunotherapy for that matter, I think we all know that not all patients really require years and years of immunotherapy. They're still trying to figure out how to use immunotherapy in these post-surgical settings, using the MRD to de-escalate adjuvant therapies. So I think we have to have some sort of strategy here. But outside of a clinical trial, I will not be using those assays here to cite treatments, but certainly an important question to ask.  Moving on to the other exciting late-breaking abstracts, LBA5, the ADRIATIC study. This is another study which was also in the plenary session. This study was designed to address this question of consolidation immunotherapy, post chemo radiation for limited-stage small cell cancer, the treatment arms being durvalumab tremelimumab, and durvalumab observation. So what do you think about the study? This study also received a lot of applause and a lot of attention at the ASCO meeting. Dr. Nate Pennell: It was. It was remarkable to be there and actually watch this study as well as the LAURA study live, because when the disease free survival curves and in the ADRIATIC study, the overall survival curves were shown, the speakers were both interrupted by standing ovation of applause just because there was a recognition that the treatment was changing kind of before our eyes. I thought that was really neat. So in this case, I think this is truly a historic study, not necessarily because it's going to necessarily be an earth shakingly positive study. I mean, it was clearly a positive study, but more simply because of the disease in which it was done, and that is limited-stage small cell lung cancer. We really have not had a change in the way we've treated limited-stage small cell lung cancer, probably 25 years. Maybe the last significant advances in that were the advent of concurrent chemotherapy and radiation and then the use of PCI with a very modest improvement in survival. Both of those, I would say, are still relatively modest advances.  In this case, the addition of immunotherapy, which we know helps patients with small cell lung cancer - it's of course the standard of care in combination chemotherapy for extensive stage small cell lung cancer - in this case, patients who completed concurrent chemo radiation were then randomized to either placebo or durvalumab, as well as the third arm of durvalumab tremelimumab, which is not yet been recorded, and co primary endpoints were overall survival and progression free survival. And extraordinarily, there was an improvement in overall survival seen at the first analysis, with a median overall survival of 55.9 months compared to 33.4 months, hazard ratio of 0.73. So highly clinically and statistically significant, that translates at three years to a difference in overall survival of 56.5%, compared to 47.6%, or almost 10% improvement in survival at three years.  There was also a nearly identical improvement in progression-free survival, also with a hazard ratio of 0.76, suggesting that there's a modest number of patients who benefit. But it seems to be a clear improvement with the curves plateauing out. In my opinion, this is very comparable to what we saw with the PACIFIC study in stage III, unresectable non-small cell lung cancer, which immediately changed practice back when that first was reported. And I expect that this will change practice pretty much immediately for small cell as well. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think it's an exciting advance in patients with limited-stage small cell lung cancer. For sure, it's practice-changing, and I think the results were exciting.  So one thing that really intrigued me was in the extensive-stage setting, the benefit was very mediocre with one-to-two month overall survival benefit in both the PACIFIC and in IMpower trial. Here we are seeing almost two-year of median OS benefit. I was kind of puzzled by that, and I thought it may have to do with patients receiving radiation. And we've seen that with the PACIFIC, and makes you wonder if both the CASPIAN and the IMpower studies actually did not allow consolidation thoracic radiation. Hypothetically, if they had allowed consolidation thoracic radiation, perhaps we would have seen better outcomes. Any thoughts on that? Dr. Nate Pennell: We've been trying to prove that radiation and immunotherapy somehow go together better for a long time. Going back to the first description of the abscopal effect, and I'm not sure if I necessarily believe that to be the case, but in this setting where we truly are trying to cure people rather than merely prolong their survival, maybe this is the situation where it truly is more beneficial. I think what we're seeing is something very similar to what we're seen in PACIFIC, where in the stage IV setting, some people have long term survival with immunotherapy, but it's relatively modest. But perhaps in the curative setting, you're seeing more of an impact. Certainly, looking at these curves, we'll have to see with another couple of years to follow up. But a three-year survival of 56% is pretty extraordinary, and I look forward to seeing if this really maintains over the next couple of years follow up.  Moving beyond the Plenary, there were actually lots of really exciting presentations, even outside the Plenary section. One that I think probably got at least as much attention as the ones that we've already discussed today was actually an update of an old trial that's been presented for several prior years. And I'm curious to get your take on why you thought this was such a remarkable study. And we're talking about the LBA8503, which was the 5-year update from the CROWN study, which looked at previously untreated ALK-positive advanced non-small cell in cancer patients randomly assigned to lorlatinib, the third generation ALK inhibitor, versus crizotinib, the first generation ALK inhibitor. What was so exciting about this study, and why were people talking about it?  Dr. Vamsi Velcheti: Yeah, I agree, Nate. We've seen the data in the past, right? Like on the CROWN data, just first like a quick recap. This is the CROWN study, like the phase 3 study of third generation ALK inhibitor lorlatinib. So global randomized phase 3 study in patients with metastatic disease randomized to lorlatinib versus crizotinib, which is a controller. So the primary endpoint was PFS, and we've seen the results in the past of the CROWN readout quoted, with a positive study and the lorlatinib received FDA approval in the frontline setting. But the current study that was presented at the ASCO annual meeting is a kind of a postdoc analysis of five years. The endpoint for the study with central review stopped at three years, and this is actually a follow up beyond that last readout. Interestingly, in this study, when they looked at the median PFS at five years, the lorlatinib arm did not reach a median PFS even at five years and the hazard ratio is 0.19, which is kind of phenomenal in some ways. At 5 years, the majority of the patients were still on the drug. So that's quite incredible. And the benefit was more profound in patients with brain mets with a hazard ratio of 0.08. And again, speaking to the importance of brain penetrant, small molecule inhibitors, and target therapy, the safety profile, there were no additional safety signals noted in the study. We kind of know about the side effects of lorlatinib already from previous studies readouts. No unusual long-term toxicities.  I should note though, about 40% of patients did have CNS, AEs grade 1, 2 CNS toxicities on the  lorlatinib arm. And the other interesting thing that was also reported in the trial was dose reduction of lorlatinib did not have an impact on the PFS, which is interesting in my opinion. They also did some subgroup analysis, biomarker testing, biomarker populations. Patients who had P53 cooperation did much better with lorlatinib versus crizotinib. So overall, the other thing that they also had shown on the trial was the resistance mechanisms that were seen with lorlatinib were very different than what we are used to seeing with the earlier generation ALK inhibitors. The majority of the patients who develop resistance have bypass mechanisms and alterations in MAP kinase pathway PI3K/MTOR/PTEN pathway, suggesting that lorlatinib is a very potent ALK inhibitor and on target ALK mutations don't happen as frequently as we see with the earlier generation ALK inhibitors.  So I think this really begs the question, should we offer lorlatinib to all our patients with metastatic ALK-positive tumors? I think looking at the long-term data, it's quite tempting to say ‘yes', but I think at the same time we have to take into consideration patient safety tolerability. And again, the competitor arm here is crizotinib. So lorlatinib suddenly seems to be, again, cross trial comparisons, but I think the long-term outcomes here are really phenomenal. But at the same time, I think we've got to kind of think about patient because these patients are on these drugs for years, they have to live with all the toxicities. And I think the patient preferences and safety profile matters in terms of what drug we recommend to patients. Dr. Nate Pennell: I completely agree with you. I think the right answer, is that this has to be an individual discussion with patients. The results are incredibly exciting. I mean, the two-year progression free survival was 70%, and the five-year, three years later is still 60%. Only 10% of people are failing over the subsequent three years. And the line is pretty flat. And as you said, even with brain metastases, the median survival is in reach. It's really extraordinary. Moreover, while we do talk about the significant toxicities of lorlatinib, I thought it was really interesting that only 5% of people were supposedly discontinued the drug because of treatment related AEs, which meant that with dose reduction and management, it seems as though most patients were able to continue on the drug, even though they, as you mentioned, were taking it for several years.  That being said, all of us who've had experience with the second-generation drugs like alectinib and brigatinib, compared to the third-generation drug lorlatinib, can speak to the challenges of some of the unique toxicities that go along with it. I don't think this is going to be a drug for everyone, but I do think it is now worth bringing it up and discussing it with the patients most of the time now. And I do think that there will be many people for whom this is going to be a good choice, which is exciting. Dr. Vamsi Velcheti: Absolutely, completely agree. And I think there are newer ALK inhibitors in clinical development which have cleaner and better safety profiles. So we'll have to kind of wait and see how those pan out.  Moving on to the other exciting abstract, LBA8509, the KRYSTAL-12 study. LBA8509 is a phase 3 study looking at adagrasib versus docetaxel in patients with previously treated advanced metastatic non-small cell cancer with KRASG12C mutation. Nate, there's been a lot of hype around this trial. You've seen the data. Do you think it's practice-changing? How does it differentiate with the other drug that's already FDA approved, sotorasib?  Dr. Nate Pennell: Yeah, this is an interesting one. I think we've all been very excited in recent years about the identification of KRASG12C mutations as targetable mutations. We know that this represents about half of KRAS mutations in patients with non-small cell lung cancer, adenocarcinoma, and there are two FDA-approved drugs. Sotorasib was the first and adagrasib shortly thereafter. We already had seen the CodeBreaK 200 study, which was a phase 3 study of sotorasib versus docetaxel that did modestly prolong progression free survival compared to docetaxel, although did not seem to necessarily translate to an improvement in overall survival. And so now, coming on the heels of that study, the KRYSTAL-12 study compared adagrasib, also the KRASG12C  inhibitor versus docetaxel and those with previously treated non-small cell with KRASG12C. And it did significantly improve progression free survival with a hazard ratio of 0.58. Although when you look at the median numbers, the median PFS was only 5.5 months with the adagrasib arm compared to 3.8 months with docetaxel. So while it is a significant and potentially clinically significant difference, it is still, I would say a modest improvement.   And there were some pretty broad improvements across all the different subgroups, including those with brain metastases. It did improve response rate significantly. So 32% response rate without adagrasib, compared to only 9% with docetaxel. It's about what you would expect with chemotherapy. And very importantly, in this patient population, there was activity in the brain with an intracranial overall response rate among those who had measurable brain metastases of 40%. So certainly important and probably that would distinguish it from drugs like docetaxel, which we don't expect to have a lot of intracranial toxicity. There is certainly a pattern of side effects that go along with that adagrasib, so it does cause especially GI toxicity, like diarrhea, nausea, vomiting, transaminitis. All of these were actually, at least numerically, somewhat higher in the adagrasib arm than in docetaxel, a lot more hematologic toxicity with the docetaxel. But overall, the number of serious adverse events were actually pretty well matched between the two groups. So it wasn't really a home run in terms of favorable toxicity with that adagrasib.  So the question is: “In the absence of any data yet on overall survival, should this change practice?” And I'm not sure it's going to change practice, because I do think that based on the accelerated approval, most physicians are already offering the G12C inhibitors like sotorasib and adagrasib, probably more often than chemotherapy, I think based on perceived improvement in side effects and higher response rates, modestly longer progression-free survival, so I think most people think that represents a modest improvement over chemotherapy. And so I think that will continue. It will be very interesting, however, when the overall survival report is out, if it is not significantly better, what the FDA is going to do when they look at these drugs.  Dr. Vamsi Velcheti: Thanks so much. Very well summarized. And I do agree they look more similar than dissimilar. I think CodeBreaK-200 and the KRYSTAL-12, they kind of are very identical. I should say, though I was a little surprised with the toxicity profile of adagrasib. It seemed, I mean, not significantly, but definitely seemed worse than the earlier readouts that we've seen. The GI tox especially seems much worse on this trial. I'm kind of curious why, but if I recall correctly, I think 5% of the patients had grade 3 diarrhea. A significant proportion of patients had grade 3 nausea and vomiting. And the other complicating thing here is you can't use a lot of the antiemetics because of the QT issues. So that's another problem. But I think it's more comparable to sotorasib, in my opinion.  Dr. Nate Pennell: While this is exciting, I like to think of this as the early days of EGFR, when we were using gefitinib and erlotinib. They were certainly advances, but we now have drugs that are much more effective and long lasting in these patients. And I think that the first-generation inhibitors like sotorasib and adagrasib, while they certainly benefit patients, now is just the beginning. There's a lot of research going on, and we're not going to talk about some of the other abstracts presented, but some of the next generation G12C inhibitors, for example, olomorasib, which did have also in the same session, a presentation in combination with pembrolizumab that had a very impressive response rate with potentially fewer side effects, may end up replacing the first generation drugs when they get a little bit farther along. And then moving on to another one, which I think potentially could change practice. I am curious to hear your take on it, was the LBA8505, which was the PALOMA-3 study. This was interesting in that it compared two different versions of the same drug. So amivantamab, the bispecific, EGFR and MET, which is already approved for EGFR exon 20 non-small cell lung cancer, in this case, in more typical EGFR-mutated non-small cell lung cancer in combination with osimertinib with the intravenous amivantamab, compared to the subcutaneous formulation of amivantamab. Why would this be an important study? Dr. Vamsi Velcheti: I found this study really interesting as well, Nate. And as you know, amivantamab has been FDA approved for patients with exon 20 mutation. And also, we've had, like two positive readouts in patients with classical EGFR mutations. One, the MARIPOSA study in the frontline setting and the MARIPOSA-2, in the second-line post osimertinib setting. For those studies, the intravenous amivantamab was used as a treatment arm, and the intravenous amivantamab had a lot of baggage to go along with it, like the infusion reactions and VTEs and other classic EGFR related toxicity, skin toxicities. So the idea behind developing the subcutaneous formulation of amivantamab was mainly to reduce the burden of infusion, infusion time and most importantly, the infusion related reactions associated with IV formulation.  In a smaller phase 2 study, the PALOMA study, they had looked at various dosing schemas like, subcutaneous formulation, and they found that the infusion related reactions were very, very low with the subcutaneous formulation. So that led to the design of this current study that was presented, the PALOMA-3 study. This was for patients who had classical EGFR mutations like exon 19, L858R. The patients were randomized 1:1 to subcutaneous amivantamab with lazertinib versus IV amivantamab plus lazertinib. The endpoints for the study, it's a non-inferiority study with co primary endpoints of C trough and C2 AUC, Cycle 2 AUC. They were looking at those pharmacological endpoints to kind of demonstrate comparability to the IV formulation. So in this study, they looked at these pharmacokinetic endpoints and they were essentially identical. Both subcutaneous and IV formulations were compatible. And in terms of clinical efficacy as well, the response rate was identical, no significant differences. Duration of response was also identical. The PFS also was comparable to the IV formulation. In fact, numerically, the subcutaneous arm was a little better, though not significant. But it appears like, you know, the overall clinical and pharmacological profile of the subcutaneous amivantamab was comparable. And most interestingly, the AE profile, the skin toxicity was not much different. However, the infusion reactions were substantially lower, 13% with the subcutaneous amivantamab and 66% with IV amivantamab. And also, interestingly, the VTE rates were lower with the subcutaneous version of amivantamab. There was still a substantial proportion of patients, especially those who didn't have prophylactic anticoagulation. 17% of the patients with the subcutaneous amivantamab had VTE versus 26% with IV amivantamab. With prophylaxis, which is lower in both IV and subcutaneous, but still subcutaneous formulation at a lower 7% versus 12% with the IV amivantamab.  So overall, I think this is an interesting study, and also the authors had actually presented some interesting data on administration time. I've never seen this before. Patients reported convenience using a modified score of patient convenience, essentially like patients having to spend a lot of time in the infusion site and convenience of the patient getting the treatment. And it turns out, and no surprise, that subcutaneous amivantamab was found to be more convenient for patients.  So, Nate, I want to ask you your take on this. In a lot of our busy infusion centers, the time it takes for those patients to get the infusion does matter, right? And I think in our clinic where we are kind of fully booked for the infusion, I think having the patients come in and leave in 15, 20 minutes, I think it adds a lot of value to the cancer center operation.  Dr. Nate Pennell: Oh, I completely agree. I think the efficacy results were reassuring. I think the infusion related reaction difference, I think is a huge difference. I mean, I have given a fair amount of amivantamab, and I would say the published IRR rate of 66%, 67% I would say, is maybe even underestimates how many patients get some kind of reaction from that, although it really is a first dose phenomenon. And I think that taking that down to 13% is a tremendous advance. I think fusion share time is not trivial as we get busier and busier. I know our cancer center is also very full and it becomes challenging to schedule people, and being able to do a five-minute treatment versus a five-hour treatment makes a big difference for patients.  It's interesting, there was one slide that was presented from an efficacy standpoint. I'm curious about your take on this. They showed that the overall survival was actually better in the subcu amivantamab arm, hazard ratio of 0.62. Now, this was only an exploratory endpoint. They sort of talk about perhaps some rationale for why this might be the case. But at the very least, I think we can be reassured that it's not less effective to give it and does seem to be more tolerable and so I would expect that this hopefully will be fairly widely adopted. Dr. Vamsi Velcheti: Yeah, I agree. I think this is a welcome change. Like, I think the infusion reactions and the resources it takes to get patients through treatments. I think it's definitely a win-win for patients and also the providers.  And with that, we come to the conclusion of the podcast. Nate, thank you so much for the fantastic insights today. Our listeners will find all the abstracts discussed today in the transcripts of the episode. Thank you so much for joining us today, Dr. Pennell.  Dr. Nate Pennell: Oh, thanks for inviting me. It's always fun to talk about all these exciting advances for our patients. Dr. Vamsi Velcheti: Thanks to our listeners for your time today. You will find links to all the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:    Dr. Vamsi Velcheti  @VamsiVelcheti    Dr. Nathan Pennell  @n8pennell    Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:  Dr. Vamsi Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus  Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Dr. Nathan Pennell:    Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron   Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi

Drs. Vamsi Velcheti and Nathan Pennell discuss key lung cancer abstracts from the 2024 ASCO Annual Meeting, including data from LUMINOSITY and ADAURA, novel therapies in KRASG12C-mutant advanced NSCLC, and the need for effective adjuvant therapies for patients with rare mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at Perlmutter Cancer Center at NYU Langone Health. Today, I'm delighted to welcome Dr. Nathan Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research at the Taussig Cancer Center. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Dr. Pennell is sharing his valuable insights today on key abstracts in lung cancer that will be presented at the 2024 ASCO Annual Meeting. You'll find our full disclosures in the transcript of the episode.  Nate, it's great to have you here on the podcast. Thank you for being here. Dr. Nathan Pennell: Thanks, Vamsi, for inviting me. I'm always excited for the ASCO Annual Meeting, and we have a tremendous amount of exciting lung cancer abstracts. I know we're not going to discuss all of them on this podcast, but even exciting Plenary presentations coming up.  Dr. Vamsi Velcheti: So, one of the abstracts that caught my attention was Abstract 103, the LUMINOSITY trial, which will be presenting the primary analysis at the meeting. So, there's a lot of buzz and excitement around ADCs. Can you comment on this abstract, Nate, and what are your thoughts on key takeaways from this abstract?  Dr. Nathan Pennell: Absolutely, I agree. This is really an exciting new potential target for lung cancer. So historically, when we think about MET and lung cancer, we think about the MET exon 14 skipping mutations which are present in 3% or 4% of adenocarcinoma patients. And we have approved tyrosine kinase inhibitors, small molecule inhibitors that can be very effective for those. What we're talking about here is actually an antibody drug conjugate or ADC telisotuzumab vedotin, which is targeting the MET protein over expression in non-squamous EGFR wild type advanced non-small cell lung cancer. The LUMINOSITY was a single arm, phase 2 study of teliso, and first of all, I think we have to define the patient population. So, these were MET over expressing non-small cell lung cancer by immunohistochemical staining. So, it included both what they considered MET high expression and MET intermediate expression, both of which had to be 3+ IHC positive on 25% to 50% of cells in the intermediate and 50% or higher in the high expressing group. They were treated with the ADC and had pretty promising results, a response rate of 35% in the MET high group and 23% in the intermediate group. Duration of response at nine months and 7.2 months in those two groups, and the PFS was five and a half and six months. So I would say in a previously treated population, this was relatively promising and potentially defines a completely new and unique subgroup of biomarker defined patients. So, Vamsi, I'm curious, though, if this ends up moving forward to further development, what your thoughts are on adding yet another biomarker in non-small cell lung cancer? Dr. Vamsi Velcheti: Yeah, I think it's certainly exciting. I think for this population, we really don't have a lot of options beyond the second line, and even in the second line, docetaxels are low bar. So,I think having more options for our patients is certainly outcome development. And I think MET IHC is relatively easy to deploy in a clinical setting. I think we already test for MET PD-L1 IHC routinely, and now recently, as you know, HER2 IHC given approval for ADCs, HER2 ADCs there in that space. So, I think from a technical standpoint, I don't see a big barrier in terms of adding an additional IHC marker. And usually, the IHC testing is pretty quick. And I think if you have a therapeutic approval based on IHC positivity, I think certainly from an operational standpoint, it shouldn't be a very complicated issue. Dr. Nathan Pennell: Yeah, I agree. This is cheap. It's something that can be done everywhere in the world. And as you said, in addition to diagnostic IHC, we're already looking at PD-L1, and probably moving towards doing that for HER2. This is really wonderful that we're moving into kind of the era of the ADCs, which is opening up a whole new therapeutic group of options for patients. Dr. Vamsi Velcheti: So, the other abstract that caught my attention was like, the Abstract 8005. This is the molecular residual disease MRD analysis from the ADAURA trial. The ADAURA trial, as you all know, is the trial that led to the FDA approval of adjuvant use of osimertinib in patients with EGFR mutant stage 1B through 3A non-small cell lung cancer. And in this trial, osimertinib demonstrated significant improvements in DFS and OS. And in this particular study, Abstract 8005, the authors looked at the role of MRD in predicting DFS in the study. And after 682 patients who were randomized, 36% of the patients had samples to look at MRD post- surgery. And in the trial the MRD status predicted DFS or event free survival at 36 months with a hazard ratio of 0.23. And the MRD status had a median lead time of 4.7 months across both the arms, both osimertinib and the placebo arm. So, suggesting that MRD could potentially identify high risk subgroups of patients post-surgery to tailor personalized approaches potentially in this population. So, Nate, in your practice, of course, we don't have a clinically validated approach yet to kind of use MRD in this setting, but if we have an option to use an MRD based assay, do you think that would potentially be an opportunity to perhaps escalate or de-escalate adjuvant strategies with TKIs in the adjuvant setting? Do you see value in using MRI assays post- surgery? Dr. Nathan Pennell: Yeah, I think this is a really important study because this is such an important topic around adjuvant targeted treatment. So, of course, ADAURA really changed how we treated people with EGFR mutant lung cancer who underwent surgical resection, because we know that the three years of osimertinib significantly improved disease-free survival and overall survival. But there's still a lot of questions being asked about, is that affordable? Obviously, we're putting a lot of resources into three years of treatment, and not everyone necessarily needs it. There may well be people who are cured with surgery alone and adjuvant chemotherapy. And then what about duration? Is three years enough? Do we need even longer treatment, or do we need shorter treatment? And up to date, we haven't really been able to tell people at risk of recurrence other than the pure odds-based risk based on their stage.   And the assay that was used in the ADAURA study was a personalized tumor informed assay based on the resected tumor. It's unclear to me whether this was just a subgroup of people that had this done or whether they tried to do it in all 600 patients and only, it looks like they were successful in about 32% of people. Maybe about a third were able to successfully have a tumor informed assay. So, the first question is, “Can you use this to help guide who needs treatment or not?” And I think what they showed was only about 4% of people in osimertinib arm in 12% had MRD positive at baseline after surgery. So probably, upfront testing is not really going to be all that helpful at determining who's at high risk and needs to be treated.   Interestingly, of those who were positive, though, most of them, or 80% of them, did go MRD negative on osimertinib. And what I found really interesting is that of those who did have a recurrence, 65% of them did have the MRD test turn positive. And as you mentioned, that was about five months prior to being picked up radiographically, and so you can pick them up sooner. And it also looks like about two thirds of recurrences can be identified with the blood test. So that potentially could identify people who are recurring earlier that might be eligible for a more intensive treatment. The other thing that was really interesting is of those who recurred in the osimertinib arm, 68% of them happened after stopping the osimertinib, suggesting that for the majority of patients, even those not necessarily cured, they seem to have disease control while on the osimertinib, suggesting that maybe a longer duration of treatment for those patients could be helpful. The problem is it still isn't necessarily helpful at identifying who those people are who need the longer duration of treatment. So, definitely an important study. I think it could be useful in practice if this was available clinically, especially at monitoring those after completion of treatment. I think as the sensitivity of these MRD assays gets better, these will become more and more important. Dr. Vamsi Velcheti: I think it's a little bit of a challenge in terms of standardizing these assays, and they're like multiple assays, which are currently commercially available. And I think the field is getting really complicated in terms of how you incorporate different assays and different therapeutics in the adjuvant space, especially if you're kind of looking at de-escalating immunotherapeutic strategies at the adjuvant setting, I think, makes it even more challenging. I think exciting times. We definitely need more thoughtful and better studies to really define the role of MRD in the adjuvant space. So, I guess more to come in this space. Dr. Nathan Pennell: Vamsi, I wanted to ask you about another really interesting Abstract 8011. This is a subgroup of the AEGEAN perioperative study for early-stage resected non-small cell lung cancer. This abstract is specifically looking at baseline N2 lymph node involvement in stage 2A-3B with N2 positive patients in an exploratory subgroup analysis. What are your key takeaways from the study?   Dr. Vamsi Velcheti: I felt this was a very interesting abstract for a couple of reasons. As you know, this is the AEGEAN trial, the phase 3 trial that was reported earlier last year. This is a perioperative study of durvalumab plus new adjuvant chemotherapy versus new adjuvant chemotherapy alone and adjuvant durvalumab plus placebo. The study obviously met its primary endpoint, as we all saw, like the event-free survival. And here in this abstract, the authors present an exploratory subgroup analysis of patients who had N2 lymph node involvement prior to study enrollment. So, in this study, they were focusing on perioperative outcomes. And one of the issues that has come up multiple times, as you know, in a lot of these preoperative studies, is the impact of neoadjuvant chemo immunotherapy on surgery or surgical outcomes. And consistently, across a lot of these trials, including the CheckMate 816, about 20% of patients don't end up making it to surgery. So in that light, I think this study and the findings are very interesting. In this study, they looked at patients who had N2 nodal involvement and of the patients with N2 nodal involvement, the surgical operability or the number of patients who completed surgery was similar in both the groups. So, there was no significant difference between patients who received durva versus chemotherapy and also among patients who had N2 subgroup who had surgery, similar proportions of durvalumab and placebo arms had open versus minimally invasive versus pneumonectomy. So durvalumab didn't have a negative impact on the type of surgery that the patients had at the time of surgery. So overall, the findings were consistent with other trials, perioperative trials that we have seen. So, the surgical outcomes were not negatively impacted by adding immunotherapy in the neoadjuvant perioperative space. So, this is consistent with other trials that we have seen. And also, the other issue, Nate, I'd like to get your opinion on is, across the board, in all the perioperative trials we have seen that about 20% of the patients actually don't end up making it a surgery. And of course, most of these perioperative trials, a lot of these patients are stage 3 patients. And my take on this was that there's probably a little bit of a patient selection issue. We generally tend to err on the side of operability when we have a stage 3 patient discussed in the tumor board, sometimes feel like the patient may downstage and could potentially go to surgery. But even in the real world, in stage 3 operable patients, what proportion of patients do you think don't end up going to surgery? Dr. Nathan Pennell: That is such an important question that I don't think we have the best answer to. You're right. All of these perioperative studies have a relatively high- sort of 20% to 30% of people who enroll on the studies don't necessarily go to surgery. And I don't think that they've done as great a job as they could in all of these trials describing exactly what happens to these patients. So in the real world, obviously not everyone would be fit enough to go to surgery or might progress in the time between when they were diagnosed and the time as planned for surgery. But probably more of them would go to surgery if they weren't getting neoadjuvant treatment, because that would be their initial treatment. The question is, of course, is that the right choice? If someone gets 12 weeks or nine weeks of neoadjuvant treatment and then a restaging scan shows that they've had progression with metastatic disease, are those really the people that would have been optimally treated with surgery upfront, or would they just have had recurrence on their first postoperative scan? So, it's really an important question to answer. I think the bigger one is, is the treatment preventing them through toxicity from going to treatment? And I think the studies have generally felt that few patients are missing out on the option of surgery because of toxicity being caused by the IO. And in the AEGEAN study, for example, in this subgroup, a slightly numerically higher percentage of patients in the durvalumab arm actually underwent surgery compared to those who got neoadjuvant chemo. So, it doesn't seem like we're necessarily harming people with the neoadjuvant treatment. But I know that this is a concern for patients and doctors who are undergoing this approach. Dr. Vamsi Velcheti: Definitely, I think having multiple data sets from perioperative trials, looking at the relative impact of IO on the safety and the nature of the surgery is going to be important, and this is a very important study for that reason. Dr. Nathan Pennell: Can I ask you another thing that I thought really interesting about this particular one is they looked at the difference between those with single station N2 and multi station N2. And I know this is one of those, should we be operating on people who have multi station N2 disease? And the AEGEAN study did include people who had multiple N2 stations where perhaps in the pre-IO era, these would have been treated with definitive chemoradiation and not surgery at all. But the disease-free survival hazard ratio was essentially the same for multi station N2 as it was in the overall population. So, has that changed the way we're approaching these patients in these multidisciplinary discussions? Dr. Vamsi Velcheti: Absolutely, Nate. I think surgical operability is in the eye of the beholder. I think it depends on which surgeon sees the patient or how the discussion goes in the tumor boards, as you know. Certainly, I think with this optionality of having a chemo IO option and potential for downstaging, kind of pushes, at least in our practice, more of these patients who are multistation, who would have otherwise gone down the chemoradiation route are now actually going through neo adjuvant chemo IO and with the hope that they would make it to surgery. So, I think it's an interesting change in paradigm in managing our locally advanced patients. So, I think it's certainly interesting, but I guess to your point, there clearly are some patients who probably should just have chemoradiation upfront, and we may be kind of like delaying that definitive chemoradiation approach for at least a subset of patients. So, at the end of the day, I think it's a lot of clinical decision-making and I think there's going to be a little bit of art to managing these patients and it's going to be really hard to define that population for a clinical trial.  Dr. Nathan Pennell: Yeah, clearly, multidisciplinary discussion, still very important for earliest age non-small cell lung cancer patients. If we move back to metastatic lung cancer, let's talk about Abstract 8510 looking at one of our newer, exciting biomarkers, which are the KRASG12Cmutant non-small cell lung cancer. So this is a study of a second generation KRASG12Cinhibitor, olomorasib, which was combined with pembrolizumab, the anti PD-1 antibody, in patients with advanced KRASG12C mutant non-small cell lung cancer. This is something that has been tried before with first generation G12C inhibitors, with some concerns about how safe it was to do that. So, Vamsi, what did you learn from this abstract? Dr. Vamsi Velcheti: Definitely, I think one of the concerns that we've had in other trials is like the cumulative toxicity of adding checkpoint inhibition to G12C inhibitors, especially the sotorasib CodeBreaK trial, where we see increased rates of grade 3, 4 transaminitis. So, it is encouraging to see that some of the newer agents have less of those issues when it comes to combining the checkpoint inhibition. So especially with KRASG12C, as you know, these are patients who are smokers, and often these are patients who have high PDL-1 could potentially also benefit from immunotherapy. In order for these KRASG12C inhibitors, in order to move these targeted therapy options for these patients to the front line, I do think we need to have substantial comfort in combining the checkpoint inhibitors, which is a standard treatment approach for patients in the frontline setting. I think this is exciting, and I think they're also like, as you know, there are other KRASG12C inhibitors also looking to combine with checkpoint inhibition in the frontline settings. So, we'll have to kind of wait and see how the other agents will perform in the setting. Dr. Nathan Pennell: Yeah, I completely agree. I think this is such an important area to explore specifically because unlike our other targeted oncogenes like EGFR and ALK, we have multiple options for these patients, both immunotherapy and targeted treatments. And if we could think about sequencing them or even combining them and if it could be done safely, I think that would be well worth investigating. There still was significant toxicity in this trial; 30% of people had diarrhea, even at the reduced dose, and there was transaminitis at sort of about 20% or so, although probably at a manageable level. But the response rate was really quite promising. And these are all previously IO and mostly G12C TKI pre-treated patients still had a response rate of 63%. And in those who were naive to IO and TKIs, it was 78% response rate. So, if it could be done safely, I think it's definitely worth pursuing this in further trials. Dr. Vamsi Velcheti: And also, there's some data, preclinical data, like looking at G12C inhibition. And also we have known with MET inhibition for a long time that it could potentially augment immune responses and could be having some synergistic effect with IO. So, we'll have to wait and see, I think. But safety is really the top in mind when it comes to combining these agents with checkpoint inhibitors. So, it's really encouraging to see that some of the newer agents may be more combinable IO. Now moving on to the next abstract, and moving on to, again, the early-stage setting. So, Abstract 8052 from our colleagues in Princess Margaret reported outcomes in early-stage non- small cell lung cancer in patients with rare targetable mutation. This is actually becoming increasingly more relevant because we are seeing at least, like with the ALINA data, with the ALK and EGFR, now with ADAURA, we know that these patients don't benefit with adjuvant immunotherapy, especially some of these rare oncogene living mutations, other than like G12C. So I always struggle with this. When you have early-stage patients, with, let's say, a ROS or a RET, where we just don't have data, and we know that those are poor actors because biologically these are aggressive tumors. So, there's a really odd clinical question to ask in terms of, what is the role of adjuvant immunotherapy? Of course, this trial and this abstract are not really addressing that. But what is your take on this abstract? If you could just summarize the abstract for us. Dr. Nathan Pennell: Sure. Well, I think this is incredibly important, and this is an area near and dear to my own heart. And that is, of course, the whole landscape of how we manage early-stage patients has changed with both ADAURA, because we now have effective treatment in the adjuvant setting for EGFR mutant patients, and now more recently with the ALINA trial for adjuvant alectinib for ALK positive patients now being FDA-approved. So, what that means is we actually have to be testing people at diagnosis even before they would be getting adjuvant treatment, and potentially before even surgery to look for these targets. We need the PD-L1 status, we need EGFR and ALK. And if you're going to be looking at these biomarkers, I think there is a reasonable argument to be made that you should be doing broad testing for all of the targetable oncogenes in these patients. There are some studies suggesting that there's value to this and identifying them for treatment at the time of recurrence. But we also know that these patients are at high risk of recurrence and probably need to be investigated, at least in trials for the adjuvant setting. So, this particular study looked at 201 resected, mostly adenocarcinoma patients, and then they basically sequenced them for all of the targeted oncogenes. And they were quite common, perhaps even more common than you might expect in an advanced population. So, 43% of them had KRASG12C mutations, 13% had EGFR Exon 20 mutation, ERBB2 or HER2 mutations found in 11%, MET mutations in 10%, ALK in 7%, ROS1 in 6%, BRAF in 5%, and RET in 2%. So quite common to find these targetable oncogenes in this particular population, perhaps a somewhat biased population at Princess Margaret Hospital, but very common. And then they looked at the outcomes of these patients without targeted adjuvant treatment. And what they found was there was a very high rate of recurrence. So, relapse-free survival was pretty high in these patients across different stages, and generally their prognosis was worse than the more common KRASG12C patients. Most of these, in particular the HER2 mutant patients, seem to have a significantly worse relapse free survival. Interestingly enough, though, that did not carry over to overall survival. Overall survival was better in those who had targetable oncogenes. And my guess is that that probably had to do with the availability of targeted treatments at the time of recurrence that may have impacted overall survival. But I do think that this particularly highlights the need, the unmet need for effective adjuvant treatment in these patients. And most of them, with the exception of KRAS and perhaps BRAF, perhaps MET unlikely to benefit from adjuvant immunotherapy, as you mentioned. And so, I think we really need to be investing in trials of adjuvant targeted treatments in these populations.  Dr. Vamsi Velcheti: Yeah, this is an area that we really don't have a lot of data. But Nate, a question for you. So tomorrow you have a patient with RET fusion, stage 2, N1 disease. What would you do? Would you offer them an adjuvant RET inhibitor? Dr. Nathan Pennell: I think I would search really hard for a trial to give them access. But if you really want to know what I think, and I'm usually willing to tell people what I think, I think the proof of concept is there. I think we know that in the setting of highly effective and very tolerable adjuvant targeted treatment in the EGFR space with osimertinib, in the ALK space with alectinib, if anything, drugs like selpercatinib and pralsetinib in RET fusion positive lung cancer in the advanced setting are just as well tolerated and easily as effective and long lasting. And so, I think if you did a trial and they are doing trials looking at these drugs in the adjuvant space, almost certainly you're going to see the same really dramatic disease-free survival benefit from these treatments, which, at least in the EGFR space, seems to have translated into an improvement in overall survival. And so if I had a stage II or a resected stage 3, especially a RET fusion positive patient today, I would definitely talk to them about off-label use of a RET inhibitor if I could not find a trial. Now, I understand that there are going to be reimbursement issues and whatnot associated with that, but I think the extrapolation is worth discussing. Dr. Vamsi Velcheti: Yeah, I think it's really challenging because some of these fusions are so rare and it's hard to really do large adjuvant trials for some of these rarer subgroups. Nate, fascinating insights. Our listeners will find links to the abstracts we discussed today in the transcript of the episode. And Nate, I look forward to catching up with you at the Annual Meeting, and again after the meeting for our wrap up podcast to discuss the practice-changing lung cancer abstracts and highlights from the Plenary Session. Thank you so much for joining us and sharing your insights today. Dr. Nathan Pennell: Thanks for inviting me. Vamsi. I look forward to touching base after we get to see all the late-breaking abstracts. Like I said, this is, I think, a year for lung cancer with a lot of exciting data, and I know we'll have a lot to talk about. Dr. Vamsi Velcheti And thank you so much to all our listeners for your time. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate and review and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Vamsi Velcheti @VamsiVelcheti   Dr. Nathan Pennell @n8pennell   Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures: Dr. Vamsi Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Making their return to the show are Drs. Jack West and Nathan Pennell, of City of Hope Comprehensive Cancer Center and Cleveland Clinic, respectively, this time to use the ADAURA trial as a springboard to discussing pitfalls and shortcomings of modern clinical trial designs. The trio go back and forth on control arms keeping pace with standards of care, studies mandating the ability for crossovers, and appropriate endpoints for adjuvant studies. Then, they highlight underwhelming clinical trial data that have led to FDA approvals, whether ADAURA featured a “known inferior agent” and an “inferior crossover design,” and whether ADAURA proved to be an “unethical” trial, among many other points of contention. Listen to Drs. West and Pennell's previous episode on the ADAURA trial from 20121. https://on.soundcloud.com/VQ4vb Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on Youtube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Drs. Nathan Pennell and Nancy Lin discuss emerging data on the growing problem of prior authorization and insurance denials in cancer care, their potentially harmful impact on patient outcomes, and what can be done to fix the problem. TRANSCRIPT Dr. Nathan Pennell: Hello, I'm Dr. Nathan Pennell, your guest host for the ASCO Daily News Podcast today. I'm the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research for the Taussig Cancer Institute. More importantly, today, for this podcast, I'm also the editor-in-chief for the ASCO Educational Book. On today's episode, we'll be discussing the growing problem of prior authorization and insurance denials, and how that impacts both providers and patients in their ability to access cancer care.  Joining me is Dr. Nancy Lin, a breast cancer medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School. She's addressed this problem in a recently published article in the 2023 ASCO Educational Book, and she's joining me today to highlight some emerging data on the possible harms from prior authorization and insurance denials, and what we can do to fix this problem.  Nancy, thanks so much for coming on the podcast today. Dr. Nancy Lin: Thank you for inviting me. Dr. Nathan Pennell: Some of our listeners may have noticed that we also did a podcast a number of years ago on a similar topic when we were with the Journal of Oncology Practice, and I was kind of hoping that prior authorizations would not be as big a problem, now, probably 8 or 9 years later, and unfortunately, it seems like it has gotten even worse.  Before we begin, I should mention that our disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.orgDNpod. So prior authorizations were, of course, originally intended as a cost control on the overuse of expensive medical care. However, in recent years, it seems like prior authorization has been extended to, more or less, all medical care, including supportive care medications and essential cancer care interventions that we need to use in almost every patient. We're also hearing more and more reports on patients who are denied coverage, and I think the doctors can sympathize with this, with their increasing peer-to-peer requests. And this is leading to patients being forced to wait to receive second-best options, impacting their out-of-pocket costs. And potentially, we all fear this is impacting patient outcomes, although we really would like to learn more about how this is really impacting their care. So, Nancy, can you talk to us a little bit about how prior auth is impacting patient access to cancer care today? Dr. Nancy Lin: Of course, we all have to acknowledge that part of the impetus for prior authorization is just the increasing cost of cancer care. There are some recent statistics that the U.S. spends over $200 billion annually on cancer care and that oncology drugs are a huge part of the overall drug cost in the nation and a large part of the oncology drug budget. So, I think we can't deny that the increasing costs of cancer care are in part driving this drive for more prior authorization. But this has costs, and there are costs in terms of direct patient costs as far as their quality of care, and also costs in terms of the health care providers and health care system.   And so we, as part of our article, actually solicited patients to provide their stories. And in fact, in our article, we have selected, with their permission, 3 patients who share their experiences. And these are experiences that, as a practicing oncologist, you'll be very familiar with. A patient wrote that she had been on capecitabine for a year, her disease is responding, and all of a sudden, on a Friday late in the day, she's told, “No, you need a prior authorization now, and you can't get your drug refilled.” And that led obviously to stress and delay and whatnot. And then another example is of a patient whose oncologist requested what sounds like next-generation sequencing, some sort of tumor panel and was denied. And the peer-to-peer here had apparently indicated that they are not aware of the data for the use of genomic testing and cancer treatment, which clearly there is a role for the use of genomic testing in cancer treatment. And in fact, we now have many articles that show that there's unequal access and, if we look at underrepresented minorities or other marginalized groups, that there is a dramatic difference in the utilization of advanced molecular testing. And then just the overall experience on patients and their families feeling like, at a time when they're sick, need to take charge of all of this paperwork and back and forth with insurers that is very stressful.   And then, from a provider or health care system standpoint, many, many hours are expended on prior authorizations for things like very new drug approvals that are maybe not on a pathway yet, or very commonly, simple things like a CAT scan for restaging of somebody who has advanced breast cancer where every scan requires prior authorization or antiemetics, or somebody receiving highly immunogenic chemotherapy and these kinds of death by a thousand cuts I think is how people in the health care experience the aspect of prior authorization.  Dr. Nathan Pennell: It's one of these things where we used to get a peer-to-peer for say, atypical reason for a PET scan, which made perfect sense, and you'd have to talk to an experienced expert to explain what you were doing and try to get a good rationale for that. And now, it's come to the point where a routine 2-month, 3-month CT scan is getting denied and having to be talking to someone who's not as experienced in this. Again, it feels still like a collection of anecdotes though in many ways. Is there any sort of published data on denials of care and prior auths and how this is impacting approvals and patient access? Dr. Nancy Lin: There are survey data, which one has to admit is not necessarily gold-standard data, but there are data from the American Medical Association, as well as a 2022 ASCO member survey. And in that ASCO member survey, over 90% of oncologists reported that they had personally experienced, in their patients, a delay in treatment related to prior authorization. Over 90% had issues getting needed diagnostic evaluations. Over 90% reported that they were, "forced to go to a second choice of therapy." And about a third of oncologists reported that they believed that the prior authorization, either delays or denial of care, led to changes or worsening of patient survival, which I think is the most concerning statistic of all.  Now, I think that one can argue that these are essentially physician self-report and what's the gold standard as far as whether there has been an impact? But I think that the fact that these reports are so prevalent means that, even if the reality is half of what has been reported, it's still a lot. And I think that  the power of these kinds of surveys is just enormous, that a high prevalence of the problems have been reported, I think, points to something even if we don't have gold standard quote data now.  Within our institution, Dana-Farber, we have done an analysis of oral medication prescribing. So, we do have gold standard and very granular data on patients that we've seen. And we've seen denials and requirements of prior authorization not only for expensive cancer medications and growth factors but also for even medicines like generic tamoxifen, which, honestly, how does that need prior authorization in this day and age? Medications like supportive care, antiemetics, and really things that ultimately, we were able to get approved 97% of the time, but [prior authorization now] introduces a delay and introduces stress. And although one may not be able to measure a so-called negative outcome from a patient recurrence standpoint, I think that there are other kinds of negative outcomes that are important, including just the experience of a cancer patient undergoing treatment, the stress of all of the denial letters and the delays that can occur as a result. Dr. Nathan Pennell: And it's not just patients. Obviously, we want to be patient-centered in our care and focus on how this impacts them. But this is also significantly impacting practitioners and cancer centers and physicians and the administrative burden of having to do the prior authorizations, which of course are not standardized in any way and vary from payer to payer and geographic area to geographic area. Is there data on how the changes in prior auth have impacted practices and physicians? Dr. Nancy Lin: Yes. In fact, there have been several surveys as well as in the practice types of studies trying to understand the staffing that is required to manage the prior authorization requests. And some of the estimates are an additional 40 hours per week per oncologist, that's a full-time position. Some of these tasks can be carried out by non-oncology-trained providers but many of them do require either the oncologist or a nurse practitioner equivalent to be on the phone for the peer-to-peer or a full-time clinical provider and you are given a 4-hour window to do a peer-to-peer in the middle of clinic, that's very disruptive. And I think that that's fine if it's every now and then for drugs that we all agree are perhaps outside of their usual indication. But if this is every CAT scan and every brain MRI and every time we prescribe an oral drug, it really does affect both clinic workflow, and just the psychology; I think it really contributes to burnout.  There was a very interesting survey actually of oncology trainees who, not even to the point where one is an attending physician, but at the trainee level indicating that this was something that was causing them a lot of distress, and in some cases, questioning the whole idea of going into medicine. And then when you think with the attrition that we're seeing in the health care workforce, we do really have to be careful about these burnout issues because we really can't afford to lose a lot of oncology staffing as the patient population ages and we're seeing higher prevalence of cancer. I think it's imperative that we take care of our oncology workforce. And I think this survey was very interesting because it went beyond the attending physician to other levels of oncology care, all of which are affected.  And there have been, as you know, many growing or nascent attempts at various residency programs to think about unionizing and what are the kinds of concerns or complaints that trainees bring up. And one of [the complaints] that  comes up a lot is, “We have to do these prior authorizations and there's all this administrative paperwork that doesn't require an entry-level person.” I'm not saying that they should or shouldn't do it - I'm not going to take a position on that - but the fact is that somebody has to do it in the current system, and whoever does it, it causes burnout. And I think that that is important. And the other piece of it has to do with equity and access to care because we're coming from academic institutions. We have a staff of people who help with prior authorization. That's not true in every practice in the United States. And I really worry about not so much denial of care but even a step beyond that, which is if you are in an under-resourced office and it's too hard to get certain things done, you don't do them because you just don't have the ability or you don't have the staffing to be able to find insurance. And I think that is very concerning to me in terms of access to care, access to some of our immune-targeted therapies, and access to the optimal support of care medications. We come from very well-resourced places as far as the administrative staff, relatively speaking, and that's just not true everywhere.  Dr. Nathan Pennell: This whole idea kind of falls under the idea of creating friction in the system to try to slow things down. I've seen data suggesting that things like peer-to-peer requests for appeals actually lead to a majority of physicians not having time or taking the time to actually do that. And that may be sometimes because they know it's indefensible and don't want to go through the process. But probably a lot of the time it's just because they don't have time to do it in their busy day and those patients then don't get their care covered. So, it's really a problem.  Now, the other thing that is really remarkable to me is, this is 2023 and everything is so technologically advanced. You can make major financial transactions electronically on your phone in just a few seconds, really complicated things. And yet this kind of [prior authorization] process really is still often done over the phone and by fax and with 100 different systems that don't talk to one another. And at the same time, oncology is becoming more and more guideline-driven where what we do actually have is really good evidence behind it. And there are even published guidelines for almost every disease and line of care about everything that we do from scan intervals to what kinds of treatment and how often and what supportive care is necessary. So, this would seem like an optimal situation for a technology solution where we tie in guidelines to what should and shouldn't be covered. What's going on out there in terms of trying to fix this? Dr. Nancy Lin: Some important questions are: Who makes the guidelines? What are the regulations as far as which guidelines insurance might adopt - their own internal guidelines or NCCN or comparable organizations? And what do you do when somebody wants to deviate from the guideline or pathway? And then finally a practical question, which is you don't really want to have a different platform and a different guideline for every insurance plan for every patient. And I think that is a little bit of even if we move to a purely electronic system, that will still be a problem.  The state of Florida had done this pilot study that tried to use or incorporate the NCCN guidelines as part of their approval or review process for prior authorization requests and at least based on the report that's published, saved $15 million in costs. And we would hope if the care was more NCCN guideline-concordant, which has been shown to improve outcomes, that would have been done without a detriment to patient outcomes. I don't think we have enough granular information to be 100% sure of that, but I would assume that that's most likely the case. I do think that some amount of guideline use could be useful.   And one of the things that we proposed in our article was the idea that one could create a sort of gold card system such that if a provider or a practice, for example, adheres to certain pre-agreed-upon guidelines or pathways more than 80% of the time, which is sort of considered good adherence and taking into account patient preference and comorbidities and whatnot, that that practice or provider could be sort of gold carded, so to speak, and actually have many of the prior authorization requirements go away so long as that is adhered to. And so that's one idea.  One of the concepts that Dario Trapani, who was the first author of our paper, put forward is that you don't necessarily need every person to be compliant with every guideline. Generally, you need for there to be compliance and that there could be different categories of treatment so that supportive care medications, pain medications for cancer-related pain, could potentially be exempt from prior authorization requirements completely. And then at the same time for other kinds of prior authorization requests, it's not enough to just change a fax form to an electronic form. That's an improvement from having faxes going back and forth by paper, but really isn't a fundamental change in the prior authorization process or vision. And so, this idea of the pathways and then only when something is deviated in some sort of major way in various categories to be determined that sort of triggers a peer-to-peer review that would both hopefully serve the purpose of reducing overuse of unnecessary or non- indicated treatments and save money. But also, in a way, I think that is less burdensome to the health care system. And I fully acknowledge that I am not a policy expert, I mostly research metastatic breast cancer, but this issue really affects us all very personally every day.   Dr. Nathan Pennell: I know you just said you're not a policy expert, but can you talk to us a little bit about what Congress and ASCO are doing to help from a legislation standpoint or a regulatory standpoint to help make this a little bit less painful? Dr. Nancy Lin: Yeah. So ASCO has endorsed the so-called “Improving Seniors Timely Access to Care Act.” And for those out there listening, particularly patients, you might say, “Well, I'm not a senior.” But it's important because how Medicare deals with issues often is then adopted by private insurers. And so starting with “Improving Seniors Timely Access to Care Act,” the intent is that it will also affect people with cancer at all age groups. But some of the provisions or the proposals are to convert to an electronic prior authorization system, to put systems in place for timely and efficient communication between providers and insurers, to ensure a process for real-time decisions that have some timeframe or timeline or deadline associated with it, to facilitate guidelines and pathway-informed decisions, and to also, importantly, be fully transparent about approvals and denials, portions that are denied, these sorts of reasons for denials, to really have transparency in that process which at the moment does not really exist. I think these are all very, very important steps with the overarching goal to promote timely and appropriate access to medications, procedures, and evaluations for oncology patients. Dr. Nathan Pennell: I'm just curious, in your opinion, do you think that there is actual inertia to try to change some of these things from a policy perspective? It can be kind of frustrating sometimes. It seems like the insurance industry has really kind of taken command of this by implementing these and we see the problems and we talk about them. But from a regulatory standpoint, it really seems like things are kind of maybe being a little bit neglected. Dr. Nancy Lin: I think that this is really something where I do think there will be some movement; maybe it's that I'm an optimist and that's what you need to be to be an oncologist.  I think that a big part is going to be really a focus on the impact on patients because although we certainly feel the impact on ourselves as providers and our staff, I don't know that that in and of itself is going to be enough to move the needle, like doctors complaining that they are having to spend too much time on the phone. I think the real impact is really related to the impact on patients. And as I said, I think that the AMA survey and the ASCO survey, those are very important because they really put the focus on [assessing] the impact on patients living with cancer.  Again, the limitations of a survey-based study are profound. And I do think that the current [White House] administration is very, very engaged in improving care for people with cancer. And in fact, part of this revised Cancer Moonshot [initiative] is not only better science around cancer and better molecular understanding of cancer but at the end of the day, if we can't get the right treatment to the right patient, it doesn't really matter how good the science is. And part of getting the right treatment to the right patient is not just training, guidelines and education. Part of it is just the practical aspect of insurance coverage as one important aspect of that. And so, I do think that there will be some movement on this because I think that it's really gotten to a point where this is not just inconvenient for doctors. I don't think that that's enough to drive anything forward personally, but I think that when you start to see impact on patients, that is really a big deal.  I was struck that one of the studies that we had identified was a study looking at over 13,000 chemotherapy requests and understanding how many were denied and why they were denied. And basically, about 11% of the requests ultimately were denied after peer-to-peer and all sorts of other appeals. And this was essentially the gold standard, so to speak. In this study was the oncologist's opinion as assessed by the so-called board certified oncologist, which is what was described in the publication employed by the insurer. We have these competing narratives and that is ultimately the problem: We have the AMA and the ASCO surveys which are survey-based asking the oncologists, and we have these data which are based on the insurer essentially as the gold standard arbiter. So it's hard to reconcile those two pieces of information because they're not really coming from the same place. And then I think you could also argue that, think about 13,000 chemotherapy requests, that means that essentially 90% were fine.  When we looked at our pathways employed at Dana-Farber where we check to make sure that our physicians are adhering to the pathways, we basically want to aim at about 80% with the idea that some patients decline a standard regimen, and we go to something else. They don't want alopecia with the idea that some patients have comorbidities, that you don't want to micromanage how oncologists are managing their patients. And honestly, in most pathway programs, we consider 80% to be pretty good. In this study, 80% were approved. And you might argue, is it worth reviewing 13,000 requests to this level of scrutiny for 90% to be approved? And again, I think that that really raises this idea of like rather than just switching a fax system to an electronic system to really rethink where's the low-hanging fruit? Where would prior authorization really serve a positive purpose? I think there are places where it could serve a positive purpose and where is it just adding unnecessary friction. Dr. Nathan Pennell: Yeah, it's a complicated picture and there are valid arguments on both sides. One of the things that is very appealing to me about the proposed legislation is requiring the payers to actually report and disclose their levels of denials and prior authorizations and this allow us to maybe take it beyond the anecdotal evidence to actually being able to document what they're doing. Because once you shine a light on things, sometimes it becomes a little bit harder to abuse the system.  Dr. Nancy Lin: Yes, I agree.  Dr. Nathan Pennell: Well, Nancy, thanks so much for coming on the podcast today to discuss this challenging problem. I know we could have talked about this for an hour or more. We really appreciate your work to highlight the impact of this problem both on providers and on patients, as well as outlining some efforts to find solutions. Dr. Nancy Lin: Great, thank you for having me. Dr. Nathan Pennell: I also want to thank our listeners for joining us today. If you value the insights you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Have a great day. Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Nathan Pennell @n8pennell Dr. Nancy Lin @nlinmd   Follow ASCO on social media:     @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  Dr. Nancy Lin: Stock and Other Ownership Interests: Artera Inc. Consulting or Advisory Role: Seattle Genetics, Puma Biotechnology, Daichi Sankyo, Denali Therapeutics, AstraZeneca, Prelude Therapeutics, Pfizer, Olema Pharmaceuticals, Aleta Biotherapeutics, Artera, Johnson & Johnson/Janssen, Blueprint Medicines, Genentech, Pfizer, Seattle Genetics, Merck, Zion, Olema Pharmaceuticals        

Caris Precision Oncology Alliance™ Chairman, Dr. Chadi Nabhan, sits down with Dr. Nathan Pennell, Co-Director of the Cleveland Clinic Lung Cancer Program and Vice Chair of Clinical Research for the Taussig Cancer Institute. Together they discuss the methodology and results of a recent JCO paper for which Dr. Pennell was a senior author: Modeling Costs and Life-Years Gained by Population-Wide NGS or Single-Gene Testing in Nonsquamous Non–Small-Cell Lung Cancer in the US. For more information, please visit: www.CarisLifeSciences.com

Guest host Dr. Nathan Pennell, of the Cleveland Clinic Taussig Cancer Institute, and Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, discuss the ATLANTIS trial and other novel therapies in advanced SCLC, NSCLC, and malignant pleural mesothelioma featured at the 2022 ASCO Annual Meeting Poster Sessions.  Transcript   Dr. Nathan Pennell: Hello, I'm Dr. Nathan Pennell, your guest host for the ASCO Daily News Podcast, today. I'm the co-director of the Cleveland Clinic Lung Cancer Program and vice-chair of Clinical Research for the Taussig Cancer Institute.  My guest today is my friend Dr. Vamsidhar Velcheti, an associate professor and medical director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone Health.  We'll be discussing key posters on lung cancer that will be featured at the 2022 ASCO Annual Meeting. Although the oral sessions tend to get the most press, we want to make sure you don't miss out on some high-impact abstracts that are presented in the poster session.  Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.orgpodcasts.  Vamsi, it's great to speak with you today.  Dr. Vamsidhar Velcheti: Thank you, Nate. It's a pleasure to discuss these 5 outstanding abstracts.  Dr. Nathan Pennell: Why don't we start with Abstract 9021, “Genomic correlates of acquired resistance to PD-(L)1 blockade in patients with advanced non—small cell lung cancer (NSCLC).” Vamsi, what were your key takeaways from this study?  Dr. Vamsidhar Velcheti: This is an important study in my opinion. This was a very large study of 1,700 patients from Dana Farber and the investigators looked at 45 specimens and matched pre- and post- immunotherapy treated patients. And they looked at the data mechanisms of resistance that were identified in 25 out of the 45 patients, that is 55% of the patients.  5 patients had acquired STK11 mutations. One patient had a KEAP1 alteration. There were several patients who had like KEAP1 SMARCA4 mutations. And interestingly, there were also some patients who developed KRAS-G12C mutation as well on the post-treatment specimens.  So, this is an interesting abstract. We typically don't do biopsies on patients progressing on immunotherapy. At this point, we don't have a standard clinical indication to do so. However, identifying these new novel mechanisms of genomic mechanisms of resistance is actually very important, because a lot of new therapy medications are being developed to target, for example, KEAP1, and could be approached to target microglobulin mutations. So, it's very important to kind of understand the mechanisms of resistance.  Dr. Nathan Pennell: Yeah, I completely agree. I mean, most of the benefits in second line in the refractory setting with targeted treatments came about through studies like this where there was broad sequencing of resistance and trying to understand and I think we're still kind of in the infancy of understanding resistance to immunotherapy, but it's a good start.  Abstract 9019 was another interesting study in non—small cell lung cancer. That was “A phase II study of AK112 (PD-1/VEGF bispecific) in combination with chemotherapy in patients with advanced non—small cell lung cancer.” Can you tell us a little bit about that study?  Dr. Vamsidhar Velcheti: Yeah, this is a multicenter phase-2 trial. This is an interesting agent. It's a PD-1/VEGF bispecific antibody developed by Akeso Bio. This is a single-arm study, and they did the study in 3 different cohorts.  One of the cohorts was patients with advanced non—small cell lung cancer who had wild-type EGFR/ALK, and they were treatment-naive. There was another cohort of patients where they enrolled patients with EGFR mutation who developed resistance to EGFR tyrosine kinase inhibitors (TKIs) and essentially progressed on osimertinib. And there was another cohort where patients were enrolled who were PD-1 refractory, they had prior PD-1or PD-1 chemo combination, and they had progressions. So, they enrolled a total of 133 patients, it was a decent-sized study, but a very early efficacy finding study.  In the cohort-1 which is the cohort that is enrolled with untreated patients with advanced non—small cell lung cancer. They had like 20 partial responses out of 26 patients that were evaluable and enrolled in the cohort, and there were 6 patients who had stable disease.  So, overall, the response rate was 76.9% and 100% disease control rate. So, this is a very small cohort and small data set. So, we have to interpret this with caution. But suddenly, a very interesting signal here for this VEGF/PD-1 bispecific antibody.  Dr. Nathan Pennell: The 40% response rate in the immunotherapy (IO) and chemo refractory patients, I thought was fairly interesting, although, as you said, very small numbers in these cohorts will have to be reproduced in larger trials.  Dr. Vamsidhar Velcheti: Right. I think there was a lot of excitement early on the IMpower150, right? With the combination of bevacizumab with chemo-theralizumab.  There seems to be some signal in terms of the addition of a VEGF inhibitor to immunotherapy. And we've seen that consistently in renal cells and other tumor types. So, I think this is a really intriguing signal. I think this definitely warrants further exploration.  So, the other interesting thing was cohort-2 where they enrolled patients who had progressed on EGFR TKIs. So, in that cohort, they had like 19 evaluable patients and 13 patients had a partial response and 5 had stable disease. So, a very respectable response rate of 68.4% and 94.7 disease control rate. So, again, very small numbers, but a nice signal here for the efficacy of the drug.  There was another cohort, which is the cohort-3 where they enrolled patients who progressed on PD-1 therapy, and they enrolled a total of 20 patients with 8 patients having a partial response, following progression on PD-1 therapy.  Dr. Nathan Pennell: Yeah, I look forward to seeing further follow-up on this. It definitely sounds interesting. Moving on to Abstract 8541. This was “Durvalumab (durva) after chemoradiotherapy (CRT) in unresectable, stage III, EGFR mutation-positive (EGFRm) NSCLC: A post hoc subgroup analysis from PACIFIC,' which of course was the study that led to the broad use of durvalumab, the anti-PD-L1 antibody after chemoradiotherapy for unresectable stage III non-small cell, but this was the post hoc subgroup analysis of the EGFR mutation-positive group. And this is a subgroup we've really been curious about whether there was a role for consolidation, immunotherapy, or not. And so, what are your thoughts on the study?  Dr. Vamsidhar Velcheti: I agree with you, Nate, that this is actually some data that I was really, really looking forward to. Before we actually talk about the abstract. What do you do for those patients? If you have an EGFR mutation patient who has stage IIIB, what do you do right now?  Dr. Nathan Pennell: It's a great question. I have a discussion with them about the potential pluses and minuses of doing consolidation durvalumab. But I actually don't always use durvalumab in this setting, because of concerns about if you're using durvalumab and they recur, perhaps there is a problem with toxicity with using osimertinib. Honestly, I go back and forth about what the right thing is to do in this subgroup.  Dr. Vamsidhar Velcheti: No, I think that's the right context. I think that's a good setup to kind of discuss the data from the trial. I'm really excited about this. And I'm glad that we have this data to look at.  So, as you pointed out, the Pacific trial, its U.S. Food and Drug Administration (FDA) approval for durvalumab in the consolidation setting for patients with stage III after chemoradiation. This has now been the standard of care for like a few years now. The problem with the study is that patients with EGFR/ALK were allowed to enroll in the study.  Typically, for most IO trials, we generally tend to see patients with EGFR/ALK being excluded. So, this trial was an exception. In this study, they actually presented a post-hoc exploratory analysis of efficacy and safety of patients who did consolidation with durvalumab, but there was a total of 35 patients of the 713 patients that were randomized in the trial. And out of the 35 patients with EGFR mutation, 24 received durvalumab and 11 received a placebo.  So, of course, you're going to interpret this data with a little bit of caution. This is a full stock analysis, not pre-planned in small numbers. In this dataset, essentially, the median progression-free survival (PFS) was not different among patients treated with durvalumab or placebo, and the median survival was also not statistically significant. Overall, there was not much benefit from adding durvalumab in this setting in patients who have EGFR mutation-positive stage III lung cancer.  Dr. Nathan Pennell: I think that tends to track along with what we who have been treating patients with EGFR mutations for years, and knowing the disappointing response rates, certainly in the advanced stage with immunotherapy, I think we were concerned that in this consolidation phase that it would also potentially be a relatively marginal benefit. I agree with you that 35 patients are too small to make any definitive conclusions, but it certainly isn't supportive of a large benefit.  Dr. Vamsidhar Velcheti: But I think I'm excited about the LAUREL study that's ongoing, hopefully, that'll give us a little bit more definitive answers as to what we should be doing for patients with EGFR mutation-positive disease. Suddenly this is a piece of information that's helpful for treating physicians to make some decisions on clinical management for these patients.  Dr. Nathan Pennell: I agree. Now moving beyond the non—small cell. Let's talk about “Final survival outcomes and immune biomarker analysis of a randomized, open-label, phase I/II study combining oncolytic adenovirus ONCOS-102 with pemetrexed/cisplatin (P/C) in patients with unresectable malignant pleural mesothelioma (MPM).” That's Abstract 8561. What were your takeaways here?  Dr. Vamsidhar Velcheti: Yeah, it's always good to see some new therapeutic options for patients with mesothelioma. This is somewhat of an orphan disease and we haven't seen a lot of advances. Granted, we have some new therapeutic options with immunotherapy now, like, there is now a standard of care in the frontline setting.  So, this particular approach with ONCOS-102 is an oncolytic adenovirus expressing GM-CSF. And this is intended to stimulate the local and systemic immune response and remodulate the tumor microenvironment.  This was a small phase 1 study where they had a CFT run-in of 6 patients and a total of 25 patients were randomly assigned to receive ONCOS-102 intratumorally with ultrasound guidance or CT guidance and they injected this oncolytic virus into the tumor directly.  They were also getting treatment with platinum pemetrexed which is the standard of care in the frontline setting. The control here was 6 cycles of platinum pemetrexed. So, they enrolled both the treatment-naive patients in the frontline setting and they also enrolled patients who will progress on a platinum doublet.  I should note that none of these patients were treated with immunotherapy. I think that's something that we'll kind of get back to and we'll discuss. Overall, from a safety standpoint, there were some expected toxicities like pyrexia and nausea which is seen in the experimental group. It's just kind of to be expected with an oncolytic virus. Overall, the 30-month survival rates were 34.3% and 18.2% in the control arm, and the median overall survival (OS) was 19.3 months and 18.3 in the controller.  So, for patients who were treated with the frontline chemotherapy, the survival rate was better with 30 months survival, it was 33.3 [months]. And in the experimental group, it was 0%.  So, overall, they also looked at tumor-infiltrating lymphocytes, they had CD4 around CD8 and granzyme B expressing CDA T-cells, and they had favorable PK from increased immune cell infiltration. So, this is very promising data but of course in a small study, and also in a population that hasn't had immunotherapy patients who are getting platinum doublet. In terms of safety, I think it looks promising. We need to see larger studies, especially with immunotherapy combinations.  Dr. Nathan Pennell: Yeah, I was impressed with the increased tumor infiltration of CD4 and CDA-positive T-cells, and the survival in the first line looked fairly impressive, although again, a very small subgroup of patients. But as you said, a standard of care these days is definitely going to involve immunotherapy. And so, I look forward to seeing combination trials in the future with this drug.  Shifting from mesothelioma over to small cell lung cancer, Abstract 8570 is “Stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with small cell lung cancer (SCLC) and intracranial metastatic disease (IMD): A systematic review and meta-analysis.” Do you think that this would influence how we approach patients with brain metastases in the small cell?  Dr. Vamsidhar Velcheti: There are some in the community who kind of advocate for SRS in small cells if they have limited CNS disease. Certainly, I'm not one of them, but I think this is an interesting study in that light like we have never had any proper randomized trial. And we probably won't have randomized trials in that setting. So, at the end of the day, I think we all kind of customize our treatment approaches based on our patients and how much disease burden they have.  But having said that, the authors here have done a pretty large systemic analysis, and they looked at 3,700+ trials, they looked at random effects meta-analysis pooled hazard ratios for overall survival in patients who received SRS in the whole brain with or without SRS boost.  What they found was that overall survival following SRS was not inferior to whole brain RT. What do we really make out of this data? I think, given the heterogeneity, we have to see how the analysis was done and the kind of studies that went into the analysis. But however, I think the bigger question is, is there a population that we need to maybe—perhaps like, if somebody has an isolated brain met, you could potentially consider SRS with a whole brain RT for better local control.  So, the authors actually look at pooled data to look at local control versus intracranial distant control. So, this is a really interesting approach that asks the question, if patients had SRS and whole brain radiation, would it actually offer adequate intracranial distant control meaning like, do they develop new lesions?  So, it does look fairly decent. But again, it all depends on what kind of studies went into the analysis. And I don't think we should read too much into it. But at the same time, it kind of raises the question: is there a population of patients with small cell where it may be potentially appropriate to give SRS?  So, that's what I do in my day-to-day clinical practice. Sometimes there are situations where you kind of do the thing that we don't usually always do like in the small cell, we always think about whole brain radiation as something that we always have to offer, but I want to hear your perspectives too.  Dr. Nathan Pennell: No, I was always taught that you never did anything with whole brain radiation in the small cell even with a solitary metastasis. For a study like this, it's certainly interesting. You wonder how much selection bias there was towards people with fewer brain metastases and perhaps being in better health or better response to systemic disease that were referred for SRS, compared to whole brain radiation.  Part of the issue is the morbidity associated with whole brain radiation is significantly more than with SRS. And now that we are starting to, for the first time, see some patients with small cell [lung cancer] that are living substantially longer with immunotherapy, it might be worth exploring which patients might benefit from having that lower morbidity from whole brain radiation. But I agree with you that I'm not sure that we know who those patients are.  Dr. Vamsidhar Velcheti: Yeah, I think this is a difficult question to answer through a meta-analysis in my opinion. But having said that, your thought in terms of proving systemic therapies, then we kind of revisit the paradigm of offering SRS to some patients may be, especially with new BiTE T-cell engager studies that are ongoing, and hopefully, if you see some positive results, that might change what we do, but it's an important clinical question.  Dr. Nathan Pennell: And finally, in Abstract 8524, we have an interesting analysis of patients with relapsed small cell lung cancer, who received single-agent Lurbinectedin in the phase-3 Atlantis trial. What do you think about this poster, and why should this be on our radar?  Dr. Vamsidhar Velcheti: Yeah, I think this has been an interesting approval, of course, lurbinectedin FDA approved, as you know, like in June of 2020, based on data from a trial that uses 3.2 milligrams per meter square dosing every 21 days in second line setting post-chemotherapy.  What happened after that was there was a trial with the combination with doxorubicin in the second line setting comparative arm in that phase 3 trial topotecan or CAV.  In that trial, it was a negative trial, the primary endpoint was not met. The primary endpoint was overall survival, and it was a negative trial. And there were subgroup analyses done in the trial. The study that is presented now is actually a post-hoc analysis looking at patients who received treatment with this combination with doxorubicin that is like a lurbinectedin with doxorubicin, who had like a total of 10 cycles of the combination, and they switched to lurbinectedin monotherapy.  So, there were a total of 50 patients in that trial. They looked at the responses and the durability of responses in that population. It's a highly select population that made it to 10 cycles and they had stable disease or better and they switched to lurbinectedin monotherapy.  So, the highlight of the abstract is the median overall survival was 20.7 months. Of course, for small cell, that's really impressive. But I think we've got to be really careful in interpreting this data. This is like a small subgroup of highly selected patients who actually benefited from the trial. My question for you, Nate, is do you use lurbinectedin in the second line setting frequently or are you still treating them with topotecan?  Dr. Nathan Pannell: We still often use topotecan. I think lurbinectedin certainly seems to be an active drug, and it has some favorable schedule of administration pretty well tolerated from a tolerability standpoint, but from an efficacy standpoint, I still haven't really seen much that makes it stand out as significantly better than older options like topotecan or irinotecan.  That being said, it is intriguing that there is a subgroup of people who seem to have prolonged disease control with this. The problem, of course, is if you already select the people who make it 10 cycles without progression, then you're already picking the group of people who are doing extremely well. So, it's not surprising that they would continue to do extremely well.  Nonetheless, it's a sizable subgroup of people that seem to benefit and it would really be nice if there was, for example, a biomarker that might tell us which patients would truly benefit from this drug compared to our other options.  Dr. Vamsidhar Velcheti: Yeah, exactly. True. Right, I mean, like all of us have patients who have done exceedingly well on topotecan and I had a patient on paclitaxel for years. So, it's really important to kind of keep that in mind when we look at these sub-proof post hoc analyses.  Dr. Nathan Pennell: Well, thanks Vamsi for sharing these important advances in lung cancer that will be featured at the 2022 ASCO Annual Meeting.  Dr. Vamsidhar Velcheti: Thank you, Nate.  Dr. Nathan Pennell: And thank you to our listeners for joining us today. If you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.    Disclosures:  Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  Dr. Vamsidhar Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine , AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen  Research Funding (Institution): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   

On today's episode, meet Dr. Nathan Pennell. Dr. Pennell is a medical oncologist, and Director of Thoracic Oncology at the Cleveland Clinic. He is also Vice Chair of Clinical Research for the Cleveland Clinic Taussig Cancer Institute. He's a proud dad and Steelers fan, and a really nice guy. I'm proud to have him on my show.

In this episode of Lung Cancer Considered, Dr. Nathan Pennell, from the Cleveland Clinic, and Podcast host Dr. Narjust Duma, from Dana Farber Cancer Institute, share information about how lung cancer care has changed in the 14 years Dr. Pennell has been in practice.

In this episode, Nathan Pennell, MD, PhD; Jamie E. Chaft, MD; and Stephen V. Liu, MD, answer questions asked by an audience of healthcare professionals during a live CCO webinar on biomarker-driven therapies for NSCLC. Topics include:Choosing between immune checkpoint inhibitor monotherapy and combination therapy with an immune checkpoint inhibitor plus chemotherapy for newly diagnosed NSCLCIncorporating newly approved immunotherapies into practiceEvolving guidelines and recommendations for biomarker testing  RNA- vs DNA-based next-generation sequencingInterpretation of NGS resultsUse of frontline TKI therapy for patients with CNS metastasesFuture role of KRAS inhibitors in the treatment of advanced NSCLCImproving rates of biomarker testing in lung cancerPresenters:Nathan Pennell, MD, PhDProfessorDirector, Cleveland Clinic Lung Cancer Medical Oncology ProgramDepartment of Hematology and Medical OncologyCleveland Clinic Taussig Cancer InstituteCleveland, OhioJamie E. Chaft, MDAssociate Attending PhysicianThoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew York, New YorkStephen V. Liu, MDAssociate Professor of MedicineDepartment of Medical OncologyLombardi Comprehensive Cancer CenterGeorgetown UniversityWashington, DCSupported by educational grants from Amgen; Lilly; Regeneron Pharmaceuticals, Inc.; and Sanofi Genzyme. For further information concerning Lilly grant funding, visit www.lillygrantoffice.com.Link to full program, including an downloadable slidesets and an on-demand webcast:https://bit.ly/3npjyyb 

To claim CME credit, visit https://i3health.com/oda-nsclc-kras One of the two major subtypes of lung cancer, non-small cell lung cancer (NSCLC) is a challenging disease to treat, with most patients being diagnosed at a locally advanced or metastatic stage. Despite the use of tumor histology and relevant molecular biomarkers to determine treatment strategies, outcomes remain poor, with a 5-year survival rate of only 24%. In this episode of Oncology Data Advisor, Mark G. Kris, MD, William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center, and Nathan Pennell, MD, PhD, Professor of Medicine at the Cleveland Clinic Taussig Cancer Institute, discuss the role of acquired resistance mutations in first-line treatment selection, the potential for central nervous system (CNS) disease, and the efficacy and safety of novel treatment options for patients with ALK-positive advanced NSCLC.

Chadi welcomes back Jack West (@JackWestMD), MD, associate clinical professor and medical oncologist, City of Hope Comprehensive Cancer Center, and Nathan Pennell (@n8pennell), MD, PhD, thoracic medical oncologist, director of the thoracic oncology program and director of clinical research, Cleveland Clinic, to the show. The task was to break down the ADAURA trial again, but to go beyond ADUARA and explore the use of various endpoints in lung cancer and how trials should be optimally designed to assure that patients garner the benefits that they deserve. The trio uses this discussion to contextualize a debate on the FDA lowering vs raising regulation on adjuvant therapies and whether the FDA should simply make drugs available and encourage physicians to use their best clinical judgment when prescribing them. ADAURA is only one study, but there are so many lessons that can be learned from the trial that can benefit current and future trial design. View Dr. West’s JAMA viewpoint on the ADAURA trial https://jamanetwork.com/journals/jamaoncology/article-abstract/2775933 View Dr. Pennell’s opposing JAMA viewpoint https://jamanetwork.com/journals/jamaoncology/fullarticle/2775934

In this episode, Nathan Pennell, MD, PhD, and Laura J. Tafe, MD, provide medical oncology and pathology perspectives, respectively, when answering questions from a clinician audience on topics including:Next steps in patient care after identifying a biomarker: selecting treatment, getting insurance approval, arranging for financial assistancePerforming biomarker testing on cytology vs surgical or anatomic pathology specimensFactors affecting turnaround time when testing liquid biopsy vs tissue specimensChoice of a targeted agent vs chemotherapy plus immunotherapy for first-line treatment of patients with RET fusions, BRAF mutations, or MET exon 14 skippingConcordance between IHC and FISH or NGS for ALK rearrangementsUse of fluid cytology specimens when testing for fusions in RET or NTRK and MET amplificationCost considerations with performing multiple single-gene assays vs upfront NGSTesting for driver mutations in early-stage NSCLCDeveloping institutional workflows to enable pathologists to order reflex molecular testing panelsPresenters:Nathan Pennell, MD, PhDProfessorDirector, Cleveland Clinic Lung Cancer Medical Oncology ProgramDepartment of Hematology and Medical OncologyCleveland Clinic Taussig Cancer InstituteCleveland, OhioLaura J. Tafe, MDAssociate Professor of Pathology and Laboratory MedicineDartmouth-Hitchcock Medical CenterLebanon, New HampshireThe Geisel School of Medicine at DartmouthHanover, New HampshireContent supported by an educational grant from Lilly.Link to full program, including an associated Podcast Pearls PDF, downloadable slidesets, and on-demand Webcasts:http://bit.ly/3a3e1Xs

One of the two major subtypes of lung cancer, non-small cell lung cancer (NSCLC) is a challenging disease to treat, with most patients being diagnosed at a locally advanced or metastatic stage. Despite the use of tumor histology and relevant molecular biomarkers to determine treatment strategies, outcomes remain poor, with a 5-year survival rate of only 24%. In this episode of Oncology Data Advisor, Mark Kris, MD, William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center, and Nathan Pennell, MD, PhD, Professor of Medicine at the Cleveland Clinic Taussig Cancer Institute, discuss the role of acquired resistance mutations in first-line treatment selection, the potential for central nervous system (CNS) disease, and the efficacy and safety of novel treatment options for patients with ALK-positive advanced NSCLC.

Jack West (@JackWestMD), MD, City of Hope Comprehensive Cancer Center, and Nathan Pennell (@n8pennell), MD, PhD, Cleveland Clinic, debate the results of the ADAURA trial presented as a plenary session at the 2020 ASCO virtual meeting, especially the extrapolation from DFS to OS, balance of chemotherapy administration in the treatment arms, lumping of varying disease stages in treatment arms, and severity of toxicity issues.

The latest episode of Lung Cancer Considered focuses on the research from the ADAURA trial that came out of ASCO 2020. This episode features a conversation between IASLC Chief Science Officer, Dr. Chandra Belani; Dr. Nathan Pennell, professor of medicine and director of the Lung Cancer Medical Oncology Program at the Cleveland Clinic Taussig Cancer Institute; Dr. Jack West, an associate clinical professor in medical oncology, a specialist in thoracic oncology and executive director of employee services at City of Hope of Comprehensive Cancer Center; and Jill Feldman, lung cancer patient, patient advocate and co-founder of the group EGFRResisters.

Dr. Nathan A. Pennell, associate professor and director of the lung cancer medical oncology program at the Cleveland Clinic Taussig Cancer Institute, shares his insight on the abstracts featured at the #ASCO20 Virtual Scientific Program that show promising advances for patients with lung cancer. Dr. Pennell is also a site investigator in the study by the COVID-19 and Cancer Consortium and discusses the findings of its first report released at #ASCO20.   Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Today I'm speaking with Dr. Nathan Pennell, associate professor and director of the Lung Cancer Medical Oncology Program at the Cleveland Clinic Taussig Cancer Institute. He is also a consulting editor of JCO Oncology Practice. Dr. Pennell will discuss key abstracts on lung cancer that were featured at the ASCO20 Virtual Scientific Program. He will also tell us about the first report of the COVID-19 and Cancer Consortium that was discussed during the meeting. Dr. Pennell was a site investigator in the study, abstract LBA-110.   Dr. Pennell reports paid consulting for AstraZeneca, Merck, Eli Lilly, Genentech, and Bristol-Myers Squibb. Full disclosure is relating to all Daily News podcasts can be found on our episode pages. Dr. Pennell, it's great to have you on the podcast today.   Dr. Nathan Pennell: Thanks, Geraldine. I'm glad to be able to talk about these abstracts.   ASCO Daily News: So what are the key abstracts that will likely change standard of care in your opinion?   Dr. Nathan Pennell: Well, I think there was one primary abstract that really should change care, although it is not yet involving a drug that's been approved by the FDA at this time. And this was in the plenary session, so this was an abstract number LBA-005, which is the ADAURA study. So this was a phase III randomized trial of the third generation EGFR inhibitor osimertinib, given as adjuvant therapy in people with stage IB or through stage IIIA EGFR mutation positive lung cancer after surgery. Patients who had early stage EGFR mutant cancer were randomly assigned after surgery and adjuvant chemotherapy to up to three years of either osimertinib once a day or a placebo once a day, and the primary endpoint of the study was disease-free survival, with a secondary endpoint of overall survival.   So this trial did fully accrue, and we've been waiting on results. And rather unexpectedly, we recently heard that the trial had been unblinded at an interim analysis, because it had already met its end point for disease-free survival. And they kind of sneaked it into the plenary session, which I thought was really good to be able to get the data out so quickly. So essentially what the study showed was that the primary endpoint, which was disease-free survival in people with either stage II or stage IIIA EGFR mutant lung cancer was significantly longer in people who'd gotten the adjuvant osimertinib versus those who got the placebo.   In fact, at 2 years the disease-free survival was 90% in the treatment group, versus only 44% in the placebo group, with a hazard ratio of 0.17. And a very impressive looking curve. So this was, I think, a very significant finding and one to certainly congratulate the authors for such a meaningful presentation.   The good thing is that it seems to have a big impact on disease-free survival I think the criticism-- so if anyone was following along on social media, you can see there was quite a bit of discussion about this trial-- is that, of course, the most meaningful endpoint in any sort of a curative trial like this is really, does the drug prolong overall survival or does it increase the chance that you're going to be cured of your cancer? And the truth is, because the trial was unblinded so early with only 22 months follow-up, we don't know the answer to that question. In fact, most of the people on the trial were probably still on drug, which has a three-year duration of treatment and it was only 22 months of follow-up.   So we won't know, most likely, for several years, whether overall survival has been impacted by this treatment. However, since the primary endpoint has been met, I think there is a reasonable chance that this will be something that could become available for us. And then we'll have to decide whether to use it.   I think that based upon this magnitude of a difference, I do think this will be practice changing, in that, if it is approved and available for use, it will be offered to patients with resected at least stage II and III EGFR mutant lung cancer.   ASCO Daily News: Dr. Pennell, are there any new agents in development that could potentially change the treatment landscape for patients with lung cancer?   Dr. Nathan Pennell: Well, there are several abstracts that are worth highlighting, I think, in this scenario, two of which actually could change practice. Although I'm not sure that they will. And the reason I say that is that even as the data was being presented in the same month, these drugs became approved by the FDA, and so therefore are ones that we can discuss about using.   So the two abstracts I want to discuss first are 9500 and 9501, which were the CheckMate trials of nivolumab and ipilimumab versus chemotherapy in advanced non-small-cell lung cancer. The first trial was an update on the phase III CheckMate-227 study comparing nivolumab and ipilimumab. So it's an anti PD-1 agent in an anti-CTLA-4 TLC for antibody in combination, versus chemotherapy in patients who had a PD-L1 expression greater than or equal to 1%. This combination is already approved by the FDA for this indication, and the update confirmed that with longer follow-up there continues to be an overall survival benefit in this population.   There's also an indication that nivolumab and ipilimumab may prolong survival compared to chemotherapy in the less than 1% PD-L1 subgroup. However, this was not one of the primary endpoints of the study, and so the indication doesn't include that. But I think that that's the population that's very interesting and that we should think about addressing in further trials.   Now, the second abstract, which was new, was the CheckMate-9LA study. And that was, again, across all PD-L1 levels, advanced non-small-cell lung cancer, were randomized to nivolumab and ipilimumab in combination with just two cycles of platinum doublet chemotherapy, the idea being that for those patients with lower levels of PD-L1 that may be adding the chemotherapy may be beneficial. And we know that from other studies of chemoimmunotherapy.   So this was an intriguing design. And, in fact, it did meet its primary endpoint of improved overall survival across all PD-L1 levels of limited chemotherapy plus nivolumab ipilimumab compared to chemotherapy alone, with a hazard ratio of 0.66 in favor of the combination. And, very interestingly, the magnitude of survival benefit appeared to be the same across all PD-L1 levels, whether it was high, greater than 50%, or even less than 1%, It really was about the same hazard ratio, in the range of about 0.6 for survival.   So this is great. It certainly offers a new option for our patients. And the FDA did actually approve it, again, in May 2020 for the combination. The major question though, with both of these regimens, is they were superior to chemotherapy, and chemotherapy is no longer considered standard of care in the United States for patients with non-small-cell lung cancer. Either single agent PD-1 drugs, such as pembrolizumab for high PD-L1 or chemotherapy plus a PD-1 agent in all other levels of PD-L1 expression is already the standard of care. And so I don't know where to put this into practice, when we already have other combinations or agents in the setting. And it's not clearly, dramatically better just looking across trials.   And so I think, while this certainly offers more options for our patients, that we'll have to wait and see if there is a patient population that would benefit especially well from one of these combinations compared to what we already have available. Certainly, the toxicity is perhaps tolerable, but perhaps somewhat more than single agent PD-1 with the combination of the CTLA-4 antibody.   Another perhaps not yet practice changing but could at some point become practice changing abstract was 9503. This was a study called the CITYSCAPE study. So these were, again, first-line stage IV non-small-cell lung cancer patients. It was randomized phase II, and they were randomly assigned to either atezolizumab, the anti PD-L1 agent plus placebo or atezolizumab plus tiragolumab, which is anti-TIGIT antibody, T-I-G-I-T, which is another immune checkpoint inhibitor. And the primary endpoint was response rate and progression-free survival.   This was for everyone with a PD-L1 level of greater than 1%. And, very interestingly, there was an improvement in both overall response rate. It was almost doubled from 21% up to 37%, with the combination of the PD-L1 inhibitor and the TIGIT inhibitor, and a longer progression-free survival. But I think what we learned in the presentation that was different from the abstract is that it seems as though this it was restricted to the subgroup of people whose PD-L1 score was greater than or equal to 50%. This is already a group for which we have aztezolizumab and pembrolizumab approved, and this had a dramatically higher response rate and progression-free survival in this group, with a hazard ratio really of 0.3 compared to atezolizumab alone.   So while this is not yet practice changing, because it's just a randomized phase II and the drug is not yet approved, I do think that this is the first signal we've seen that there may be a subgroup of people with a high PD-L1 that may benefit by adding a second immunotherapy drug. And this is well worth proceeding to a phase III trial.   And then, finally, of the agents that are potentially practice changing in the relatively near future would be abstract 9504, which was the DESTINY study. This was a single agent phase II trial using trastuzumab deruxtecan, which is an antibody drug conjugate against HER2. And this was looking specifically in a cohort of patients with HER2 mutated metastatic non-small-cell lung cancer.   There were 42 patients in this cohort that were treated with the antibody drug conjugate. All of them had been pretreated with chemotherapy and/or immune checkpoint inhibitors. And very promisingly, we saw a 62% response rate with this agent, which was really probably the highest response rate we've seen of any drug in this population of HER2 mutant lung cancer.   We know that HER2 mutant lung cancer is an identifiable population of adenocarcinoma patients. It's about 2% of adenocarcinoma patients. But for the first time, we finally saw efficacy in this population with a targeted drug. Because tyrosine kinase inhibitors have been disappointing in the past. So this drug showed a 62% response rate and, very promisingly, and estimated progression-free survival of 14 months. Very comparable to what we might see with, say, an EGFR tyrosine kinase inhibitor in mutant lung cancer.   So I think this is very promising and certainly deserves consideration for our patients with HER2 mutant lung cancer. Importantly, it also was fairly well tolerated. Now, there were some patients who got interstitial lung disease from the treatment, but all of them were grade 2 and responded to steroids. And so I think that this would be not a deal breaker in terms of toxicity. And hopefully we're soon going to have to add HER2 to our list of targeted agents that will have to be testing for in non-small-cell lung cancer.   ASCO Daily News: Well, we also heard some promising news about a randomized trial for patients with oligometastatic lung cancer that could potentially affect standard of care. Can you tell us about this study?   Dr. Nathan Pennell: Yes. I think you're referring to the SINDAS study, which is abstract number 9508. So this is basically building on what we know about patients with so-called osimertinib disease. Which means that really only a few sites of distant metastatic disease. We know from trials in non-small-cell lung cancer -- and so far, just to point out, these trials are all small phase II trials -- that by doing definitive either surgery or radiation to limited sites of metastatic disease in addition to systemic therapy, that patients may actually have longer control of their cancer and may even live longer. And this is being hopefully replicated in a phase III trial.   Now, the particular trial, the SINDAS study, was looking at the EGFR mutation positive subgroup of lung cancer patients. So this is about 15% of adenocarcinoma patients. These are treated preferentially with tyrosine kinase inhibitors, which have been shown to be more effective than chemotherapy. And in this study, 133 patients who had five or fewer distant sites of metastatic disease were randomly assigned to either a tyrosine kinase inhibitor, using the first generation inhibitor, such as gefitinib or erlotinib, or the same tyrosine kinase inhibitor plus stereotactic radiation -- so ablative treatment to all of the sites of disease plus the primary tumor. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival.   And while it is not surprising that this prolonged progression-free survival, because that's what we've seen consistently with this model, interestingly, there was a significant improvement in overall survival as well, with the hazard ratio of 0.68 with the addition of radiation. They did give us some breakdown of the different characteristics of the patients, and it did seem as though the number of metastases mattered. And so this might be something that could be considered more in patients who have less than two sites of disease. So really, as we know from oligometastatic disease, patients who have a single site of metastasis seemed to do better with ablative therapy, and that seems to be replicated here.   So is this practice changing now? Well, it certainly is consistent with the other phase II trials of a ablative radiation plus systemic therapy improving survival. I would like to see this replicated in a larger study before I would do this routinely. However, especially in someone who would, say, have a single site of metastatic disease, I think it would be very reasonable to consider doing radiation to that site now, based upon this data, while we're waiting for more evidence to emerge. I'm not sure I would run out and start radiating those with, say, five sites of metastatic disease, because I'm not sure that really necessarily meets the oligometastatic definition in my mind.   ASCO Daily News: And, finally, you are part of the COVID-19 and Cancer Consortium, which shared its first report at the Special Clinical Science Symposium on COVID-19 and Cancer. Briefly, how does the report shed light on the potential outcome of patients with cancer who also have COVID-19?   Dr. Nathan Pennell: Now, this, I think, was very exciting, mostly because it illustrates just how well we all come together in an emergency situation. So this was a grassroots consortium, the COVID-19 and Cancer Consortium, that was first started by some investigators at Vanderbilt University, but it came together with colleagues on social media. And before they knew it, they had gathered investigators from 100 different international sites to try to enter information on characteristics of their cancer patients who'd been infected with COVID. Because we were seeing results coming out of China suggesting that cancer patients maybe were at higher risk of both getting COVID and also having poor outcomes, and we really wanted to know how we could best serve our own cancer patients in the United States.   So in a tremendously short period of time, this consortium came together. And then they presented the results on Saturday of more than 900 cancer patients who had also been infected with COVID. Very interestingly, and concerningly, there was a 13% overall rate of mortality among patients in the cohort, suggesting that patients of cancer certainly are potentially at higher risk of dying than patients without cancers in overall infection rates. However, we had enough numbers to be able to pick out which patients may be at higher risk and not just all patients who'd had a history of cancer.   Those who had a history of cancer but that was in remission and did not appear to be current did not seem to be at any increased risk of bad outcomes, which was very reassuring. While patients who were older, who had significant conditions-- so COPD, heart disease, et cetera-- and especially those whose cancer was active and getting worse, seemed to do significantly worse and have a higher rate of dying from COVID. And so this really helps inform, for us, which patients we need to be most cautious of and would have the highest risk if they were to become infected with COVID-19.   ASCO Daily News: Well, thank you, Dr. Pennell, for sharing the highlights of that report. And we'll continue to follow the important work of the COVID-19 and Cancer Consortium. Thank you very much, Dr. Pennell, for sharing your insights with us today on the ASCO Daily News podcast.   Dr. Nathan Pennell: Thank you, Geraldine. And I really appreciate the opportunity to discuss this.   ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the podcast, please rate and review us on Apple podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Dr. Nathan Pennell, Dr. Muhammed Beg and Ms. Erin Williams discuss improving the time-to-activation of new clinical trials at an NCI-Designated Comprehensive Cancer Center. Read the article: https://ascopubs.org/doi/full/10.1200/OP.19.00325   TRANSCRIPT [PIANO MUSIC PLAYING] DR. PENNELL: Welcome to the latest Journal of Oncology Practice podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org. My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. Today, I'd like to talk about clinical trials, specifically the complex process that goes into opening a clinical trial and the surprising amount of time and individual steps that go into what might otherwise seem like a straightforward process. And while we all agree that trials are critically important for patient care and making scientific advances, as a clinical investigator, I can tell you that they can be quite a challenge to open and sometimes take a surprising amount of time and resources, which can be frustrating. With me today to discuss this topic are Dr. Shaalan Beg, associate professor of medicine in the division of hematology and oncology at the University of Texas Southwestern Cancer Center, and Ms. Erin Williams, associate director of clinical research operations at the Simmons Comprehensive Cancer Center. We'll be discussing their paper, "Improving the Time to Activation of New Clinical Trials at an NCI-Designated Comprehensive Cancer Center," to be published in the November 2019 JOP. Welcome, Shaalan and Erin, and thank you for joining me on the podcast. DR. BEG: Thanks for having us. DR. PENNELL: So can we start off by talking a little bit about what's involved in the clinical trial opening process and why this ends up being such an important issue that leads to projects, like what you describe in your paper? DR. BEG: Yes. It's a pretty complicated process. And I think I say it a lot, like, how a bill becomes a law. So how does a trial protocol become an open clinical trial available to our patients? So when you have a document which embodies the principles for the clinical trial or the clinical trial protocol, you have a consent form that will be a patient-facing document that the patient sees, which summarizes, in layperson's terms, what the procedures will be for the study. And then these documents have to go through multiple steps of approval within individual institutions. For example, the institution review board will look at the document in terms of risk management or risk assessment for the institution. Scientific committee will review the scientific integrity and see whether it suits the patients that that specific center is taking care of. And then, in parallel, you have a group of experts who want to see if that trial is something which they can feasibly execute. So hypothetically speaking, if a trial needs treadmill tests, do we have a treadmill to actually do that? So really the rudimentary, sometimes, feasibility questions. And then, as the studies are becoming more complicated, some of these studies have biomarkers which we want to identify patients for, and we need to test patients before we can find the right patients for the clinical trial. So that entire process is becoming more and more complicated. DR. PENNELL: That all sounds like it makes perfect sense, but I know a lot of our listeners might be surprised to learn that this entire process from beginning to end can take a long time-- sometimes six months or longer. What are the consequences to an institution of taking a long time to activate a trial? MS. WILLIAMS: So this is Erin. Well, the consequences can mean our access to clinical trials, right? So it can also mean access for patients to the clinical trials. So both of those things. If we take too long to open the study and a lot of other centers around the country or around the world have a study open-- and specifically, there are a lot of trials that are open internationally, and sometimes it's easier to open trials internationally more quickly-- then our patients lose access to those trials as the spots for enrollment fill up and the study goes closer and closer to its enrollment target. But in addition, sponsors, industry sponsors, pharmaceutical companies that are bringing trials to their cooperative groups in which we participate-- these are NCI-funded large-cluster groups for phase III clinical trials, we participate with those as well-- they're looking at how long it takes us, as an institution, to activate a new study. And if we start to take longer than most other institutions, they may not favor us for a particular trial to offer that trial to us. DR. PENNELL: This is such an important process, and I think this is really going to resonate with lots of people who work at centers that open clinical trials. So why don't you take us through the process? So what exactly did you do there? MS. WILLIAMS: So this is Erin again. We convened a group of stakeholders, along with a leader from our institution's Lean Six Sigma program, to really map out the process. So we convene about four or five hours of a day for everyone to come in. And it didn't just include cancer center stakeholders, but it included stakeholders from our sponsored programs administration office at the institution, our institutional review board, human research protections office, our hospital review committee. We really wanted to gather together all those people who touch the process in some way throughout the course of the time to activation. And so really with Patrice's help, who is our Lean Six Sigma expert, she really kind of started the process out, and we did kind of what your traditional Lean Six Sigma mapping might look like-- use sticky notes and words on sticky notes, mapping out the process on the long board, and then ultimately creating what the map looks like. And I think what it did was allowed everyone who was in the room to really take a look at the process and how sequential everything came out to look. One of the biggest impacts that we identified and that we highlighted in the paper is what you really saw was this gap between our scientific review committee submission and the IRB review, and then everything else in the process, because a lot of steps hung on IRB approval and didn't want to move forward, including hospital review, contract execution, things like that, until the IRB had given their stamp of approval, which of course is the review board for patient safety. So what we tried to do is, immediately, you could kind of see this visible gap in-between the steps, and that really showed us that potentially aligning that scientific committee review with the IRB review and allowing that IRB approval to happen more quickly might trigger some of the other steps. DR. PENNELL: One of the things that I found really interesting when you were talking about the various steps in the process was when you chose to start the clock, because I know that there is a lot of attention paid to how long it takes to open trials. And, you know, in my experience, I have heard that there are institutions that somewhat game their numbers by not starting their clock to opening until they've actually gotten a lot of steps already done before they do, say, a regulatory submission. And then it looks as though they're opening the trials quite quickly, but they may have already had the protocol for many months ahead of time, working on things ahead of this. And you guys chose to start from the time you actually receive the regulatory packet and the protocol to start, which makes sense. I mean, that's really when, I think, you, as an investigator, would think the clock would start. But did you ever get any pushback from your leadership or others to starting that early? DR. BEG: No. I think it's a matter of being consistent with how we report our numbers. Similar to you, we are an NCI-designated center. We report these to our advisory boards and to the NCI in regular intervals. I think whenever we're measuring numbers and we set metrics for any target, we run the risk of people trying to cut corners and gaming the system to make the number look good. I think that's pretty well-documented in any industry. And our time-to-trial activation has become this shared quality metric across the cancer center, across the institution. And we were worried that it may start being that way, that folks are trying to, "well, should we take out the weekends, those aren't really work days, or how about the time the sponsor has the packet, or--," you know? And I think, as humans, we all have tendencies to try and come up with ways to make our numbers look better. But the advantage of publishing this to a journal like the JOP with transparency on how we're measuring it, and, you know, I think we had faith that our audience would recognize when our time is-- when our time clock is starting. And there wasn't any pushback. MS. WILLIAMS: I'll just add to that. The reason why I think it's so important to be transparent with these numbers is because-- being in an administrative role and an operational in a clinical research office for a long time, investigators who are bringing a trial forward for us to activate, the calendar has started as soon as they bring me a trial that they want to open. And if I tell them that a study only took 60 days to open, and their recollection is nothing near what I'm telling them my metric is, then they're not really going to trust what I'm telling them overall. And I think it's important that I recognize, and that we recognize as an operation, that what really matters is that once we get the study, we're starting the process. It just makes the numbers more useful to you, internally. It makes it more useful to the outside companies or organizations that you're working with. And, you know, even the non-value added time that's not in your control can sometimes-- you can intervene in that. You could potentially escalate things if you haven't heard from a company in a certain period of time. So I completely agree. That makes perfect sense. DR. PENNELL: So, well, why don't we dig into your results? So what did you find through the mapping process? DR. BEG: I think one of the issues was how we can move some of the steps that happened in parallel or that happened sequentially to try and make them work in parallel. And like Erin mentioned earlier, just mapping out the process and having the different offices represented on campus that are a couple blocks away from each other really think about how they-- when they start their clocks and why they wait for specific milestones to start a review process was very helpful. So one of the steps was to really move from a sequential process of scientific review followed by an institution review board review into a process where we move that in parallel to each other. And different centers have grappled with this question in different ways. The way we decided to address this, we didn't want the IRB to be bogged down by a study that wasn't scientifically valid, that may have concerns, or is not novel enough. But we have internal data that our scientific review committee-- and this is published data-- that our scientific review committee very rarely changes the design or the structure of an industry-sponsored clinical trial, for example. So we decided that we would come up with a process where the IRB will physically review the study at a time after the scientific committee has reviewed the study. If the study is disproved, then it falls off the IRB's docket. But if it's approved, then they will be ready to review it. And we were able to shrink that time from scientific review to IRB quite significantly by modifying that process. We talked about institutional studies, so studies that our own investigators are developing. Those studies do tend to get more criticism at the scientific review committee. Our committees review them much more closely and have much more impact on those. And we decided to move them forward on a case-by-case basis. So it really required some restructuring. MS. WILLIAMS: One of the other things that we outlined in the paper, one of the other outcomes, was that our hospital review committee agreed to review the study in parallel with the IRB and in the PRMC review process and just hold their approval until those approvals had been received. And that happened. And if you looked at the individual time to getting that hospital review committee approval immediately following the intervention, it went down significantly. As with anything, it takes consent kind of massaging and working with those groups. And some of the offices and the infrastructure around clinical trial changed subsequent after we had our time to activation. And so with any of that change, processes start over, people start looking at things over again, and they decide, well, wait, why are we reviewing this in parallel? Or these other groups of people need to be reviewing this in more detail. Having said that, as those processes have changed, what we've heard and what we've experienced with those stakeholders in the institution is that their eye is always on the activation timeline. And that if we report to them, hey, this time to review committee approval has kind of gone back up, it's creeped back, and we really need to look at this again, you can see their immediate response is, oh, absolutely, we understand, these are kind of some shifts that we made, but let's get together, let's look at it, we really are hoping to push it back down. DR. PENNELL: Well, I think that's a great point to point out, that this is not a one-time thing. And whatever changes you institute, you can't just do it once and then expect it to be a permanent change if you don't follow up and ensure that it's still working. DR. BEG: One of the other things which came up when we were looking at our numbers was to figure out how to staff different positions. And there are some steps of the activation process that are very nuanced, really require special expertise. And an example for that is the coverage analysis evaluation, where a third party independent of the investigator's team decides whether every procedure or blood test or scan gets billed to insurance or is that something that gets billed to the study. So is it a research procedure or is it a standard of care procedure? And in oncology, where philosophically we view research as embedded within standard of care, that can be a pretty tricky determination to make. So the people who do this come in with a really unique set of expertise from their clinical-- that have clinical expertise and research expertise. And one of the things we noticed was for positions like those and for positions other than that, it's really important to have redundancies in those positions, so if there is staff turnover of any kind, that that process can keep moving forward. Because those are steps that-- it's hard for a consultant to come in and fill in and those people don't really just hang out on campus for us to be able to tap their time and to start processing those studies. So other than looking at our processes, it did come down to staffing those positions and making sure that we create some redundancies in those positions so that we're not completely dependent on, for example, one person for a task like that. DR. PENNELL: And that is such an obvious issue that I think maybe a lot of people may be shocked to hear that institution's administrations don't always agree that you need more than one person to do a task. But again, this is really resonating with me personally, because we went through this same issue. And there are so many important things that for some reason there's always just one person who can do it. And if they're out for whatever reason, or they leave and there's staff turnover, things just grind completely to a halt. And so I think that that's a wonderful illustration that hopefully will be convincing. Did all of this work end up making a difference in your time to opening trials? MS. WILLIAMS: It is making a difference. We are seeing improvements in certain steps of the process. We've definitely seen an improvement in our time to both scientific committee review approval, our time to IRB approval. Our coverage analysis timeline has been very steady. Our time to activation for our national cooperative group studies has been very stable at around 90 to 100 days, since instituting just kind of these simple-- well, not so simple-- but since instituting this whole process. Where we still have challenges is in our budgeting and contracting process. However, again, since we've got that institutional buy-in, it was actually our sponsored programs administration office contract director who approached me about two or three months ago and said, you know what, we really need to talk about the workflows between covered analysis, budget negotiation, and contract, because I see things kind of being an issue for us, as far as getting expedited approval and execution of contracts. So we had another about 2 and 1/2 hour meeting just about a month ago to sit down and go through that workflow and identified, again, a couple of key places where we can bring previously sequential steps into a parallel-step process. And so once again, I think the take-home of the exercise that we performed is that we have institutional stakeholders who aren't necessarily just waiting to hear from us to figure out how we can do better, but are coming to us and identifying timelines and being able to work together to continue to make those happen. DR. PENNELL: And it sounds like this has worked very well for your institution. But you point out in your manuscript that a lot of the processes are so unique to individual institutions that it's hard to make blanket recommendations that apply everywhere. So what can other sites who are also worried about their time to activation take from your process? DR. BEG: I think one message is to know what your internal process is. And I think a lot of folks who are listening to this podcast will admit that at their centers there's no one document that really maps out the entire process. So for us, the process of mapping out the trial activation process was probably the most transformative bit, the rest sort of just fell into place. DR. PENNELL: Shaalan and Erin, thank you so much for joining me on the podcast today. DR. BEG: Thank you very much. MS. WILLIAMS: Thank you. DR. PENNELL: Until next time, thank you for listening to this Journal of Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JOP's podcasts are just one of ASCO's many podcasts programs. You can find all recordings at podcast.asco.org. The full text of this paper will be available online at ascopubs.org/journal/jop in November 2019. This is Dr. Nate Pennell for the Journal of Oncology Practice signing off. [PIANO MUSIC PLAYING]

Nathan Pennell, MD, PhD, and Chadi deliberate on some timely topics in non-small cell lung cancer treatment just before the World Lung Conference convenes, including screening, adjuvant therapy, metastatic disease, and ensuring patient adherence to oral therapies.

Dr. Pennell and Dr. Kircher discuss the push for increased price transparency among stakeholders in an effort to control the rising costs of healthcare. Read the related article on ascopubs.org.   TRANSCRIPT: Welcome to the latest Journal of Oncology Practice podcast, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org. My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. Americans are very familiar with comparison shopping for goods and services based on the price. I can buy anything from a car or a television to life insurance to hiring a contractor to remodel my home. And I could expect that the price of that good or service is going to be easily available. It's going to be accurate. And then I can compare it to their competitors prices. So I can then make my decision based on that price and the quality of the goods or services. But what if you wanted to shop around for your health care? How easily can we determine the true out-of-pocket costs for, say, a hip replacement or a screening colonoscopy? In truth, I bet aside from a purely cosmetic procedure, most people don't ever recall being told what the price is of a medical procedure before having it done. So why is medicine different? And how does this impact the cost of health care? And what can we do to improve price transparency? With me today to discuss this issue is Dr. Sheetal Kircher, associate professor and GI medical oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Dr. Kircher is a member of the ASCO Health Equity Committee and was a recent ASCO Health Policy Fellow from 2018 to 2019. We'll be discussing her paper, "The opaque results of federal price transparency rules and state-based alternatives", to be published in the August, 2019 JOP. Welcome Dr. Kircher, and thanks for joining me today. Thanks for having me. So first of all, can you briefly kind of review why aren't health care costs like other goods and services? And why isn't it easy to understand and compare between them? There's a lot of reasons that health care costs are really just fundamentally different than really almost any other goods or services that I can think of. Taking your example of shopping for a TV, when you know which TV you want, you to go to multiple stores. You check to see if there's free online shipping. And you choose the lowest price. Even if you don't know what TV you want, you can see what the cost is going to be. And this cost is going to be inclusive of tax, shipping. And you can even see what that cost will be if you had a coupon or promo code. In addition to the cost of these TVs, we will see ratings, hundreds, thousands of people with commentaries on their experience with that exact product. So many times, you could even return it. So as we can see, health care is just really different. The stakes are higher. So even when we use this word, cost, shopping around for health care, and things like that, already that kind of seems like a misnomer. For the individual case and the actual cost of a service, it's complicated. It's difficult to figure out because almost nobody pays what we think of as like the list price. The literal list price for hospitals is called a charge master. A charge master is really just the list prices out the gate that a hospital comes up with and becomes a starting point for negotiation for payers. And then each plan will have a different contracted rate for that service. And this is problematic, isn't it? Because the charge master is sort of the-- when people start, at least say with the federal regulations, that's the price that they're sort of trying to get people to put out there. But that's not necessarily all that helpful. Exactly. And you know, in addition, because there's such variation in what the patient will actually pay at the end of the day after their insurance coverage kicks in, when you look at the hospital list of prices, it's difficult, even for myself with a medical degree, to understand what I'm looking at. For example, if I'm thinking of a single service, like a colonoscopy, there could be many components to a colonoscopy, such as the doctor fee, facility fee, pathologist, anesthesiologist. So even if you saw the word colonoscopy on one of these lists, it's impossible to really know if that's inclusive of all the components of that procedure. So say a patient was able to actually get a hold of these contracted rates instead of the lowest prices. And then they were able to know all the components of that service. They would still need to understand the specific cost sharing details of their insurance plan, such as like how much the deductible is, what's their copay, what's their coinsurance. In my experience, and I think it's well-published in the literature, that most patients even struggle to just know what the definition of those things are, like your deductible, let alone what their actual amounts are. You know, it does sound complicated. And obviously, I think a lot of doctors are familiar with the multiple different charges and whatnot. But at the same time, given the complexity of modern technology and whatnot it doesn't sound to me undoable for a particular hospital to bundle all of the costs of a single procedure together and to somehow link to what your insurance company should cover for that kind of thing. It does not seem to me like this is an undoable technological fix if someone wanted to do it. I agree. There's been a lot of attempts, both at the state level and federal, to really address this issue. I mean, even taking a step back even further, institutions have tried to, at least for their patients, provide more accurate down at the patient level estimates of their costs. And as simple as it sounds, it is actually quite difficult. And the reasons are because a lot of people contracting from payers as well as insurance it still is very opaque, even in people that are highly skilled and trying to figure this out. So if you are an actual patient, I mean, I think that the challenges just become even greater. But some states have taken some more kind of in the weeds active approach to improve price transparency in health care as a whole, including oncology. [INAUDIBLE] states have implemented or at least passed laws where they create something called an all-payer claims data set or APCDs. What these are it's still a list of prices. I think it tackles some of these issues that we just talked about, because what these lists are, they account for the negotiated price, as opposed to the pre-negotiation charge master. So basically, it's the price after the coupon. You know, it's like the real price. Most of these data sets, or at least many of them, have incorporated quality metrics. Now, I would have to say that the quality metrics between states is all over the map. Nobody has agreed on these quality metrics. But it's at least one more tool to help the patient in addition to cost to make decisions. I think a kind of interesting point this all brought up as we were doing this work is almost like a bigger question of do patients want to comparison shop for their health care. So I mean, if my primary care doctor, who I trust and I know, and I've known for 15 years, recommends a procedure, so say a colonoscopy, I'm likely to choose the doctor and the facility that she recommends. I don't even remember if you go to get a procedure, they usually don't even tell you ahead of time what the cost is and ask you if that's something you're interested in paying. Usually you just schedule it, and you do it. And you get a bill after the fact. That would have to be a pretty big shift in the culture of how we approach paying for health care if we were going to start comparison shopping. You'd have to understand that you needed to do that to begin with. You'd have to know how to do it and how to compare these things. It's certainly not undoable. It's something, again, that we do for almost every single other thing that we buy, but it would require quite a major change. Absolutely. And there's an even larger price transparency kind of movement going on. In relation to we were just saying about a patient-- say an oncology patient is starting chemotherapy. Federally, there's multiple different efforts that are trying to improve price transparency. So the oncology care model, one of the 13 kind of pillars of that care plan, one of them is delivering out-of-pocket costs before treatment starts. Now, in oncology specifically, this is problematic and very challenging. You know, kind of trust me, we've tried. And we continue to try because when you think of the drugs we give oral chemotherapy, targeted agents, and then IV chemotherapy, we're not only dealing with totally different modes of treatment. We're talking about different payment structures of how cost sharing works. So typically, IV chemotherapy is on our hospital outpatient benefits, while oral chemotherapy is covered by our prescription drugs. Now, both of those, in say Medicare for example, are completely different cost sharing structures. So the experience for a patient picking up their oral chemotherapy is at essentially a retail pharmacy or if it's perhaps a specialty pharmacy. But there's a cash register. And you're paying for it there. The experience of paying for your IV chemotherapy is just like you described with the procedure, where you get it done. You get the bill at home. And just the experience alone is really different. So federally, for this specific charge master display, so as of January 1st, all hospitals must publicly display their charge master. You know, like I said, these were never intended for consumer viewing. So they were first mandated to exist in the actually the Affordable Care Act. And the Trump Administration has really built upon this and said, why make patients ask for the charge master. How about we just require the hospitals to publicly display these? So that's where this kind of mandate came through. It's interesting because as we went through this exercise in the publication, and the codes they use, the abbreviations, even with a medical degree, I had a hard time deciphering what they said. Yeah, it does seem as though a lot of hospitals did not take this as a mandate to try to make this a transparent and useful thing. They said, well, the requirement is we're going to put it up. And here's our Excel spreadsheet or our PDF with all of the jargonese there. And you can do with it what you will. Absolutely. And I wasn't surprised when we saw that even within four months of this being mandated, 88% of the hospitals we looked at in Chicago had it published. They were right on it. They had published it. And it was on their website. Because the ACA had already required that they have it. So really, they just took it out of the file folder and put it on the website without much thought that they were trying to make it helpful for patients. A lot of disclaimer that a lot of, I think, hospitals overall did a really good job of putting kind of the fine print on there and saying that please speak to your doctor and facility to actually get the real cost. So I think the hospitals overall did a pretty good job of that. As you and your authors point out, if someone actually did try to use that information to comparison shop, or what I would think perhaps would be more common, they would look it up just to see what the price is going to be forwardly placed they've been told they're supposed to go. They might see a $3,000 charge for their CT, which might have been completely covered by their insurance with no out-of-pocket expense to them at all and decide not to get it because they're afraid they're going to be charged $3,000. Right. So in the hopes of having this transparent playing field, my major concern is even I, if I saw that amount of money, maybe that would make me pause a little bit actually. And I think the last thing we need to do, especially in these screening tests that there is no shortage of data saying that they improve survival. I want my patients to get them. There's enough barriers, I think, to getting someone a colonoscopy, that I would hate for that to be an unintended consequence of showing people the cost, especially in this inaccurate kind of forum. So what can we do about this? What do you and your co-authors recommend to try to address cost transparency moving forward? I think it's exciting that there is momentum here. I mean, I think price transparency, although has become a buzz word, it is going to continue to be an active issue at the state and federal levels. What makes this exciting to me is that it is bipartisan. So we all care about health care, to a different degree, and we all have different strategies. But I do feel that this is a bigger discussion about transparency, not only here at the patient level, provider level, hospital level even. I really think I hope we're moving to a place where there is a bigger discussion of transparency at all levels. I'm talking even starting up at the manufacturer level. But from a very practical patient level standpoint, we all encourage people to develop APCDs. There's interesting results that have been shown in some states that there is a good way to show people cost. And by doing so, programs, such as California's program, has actually shown that utilization of lower priced facilities has increased. And most importantly is that when patients are shown a cost and have some sort of way to impact or influence the amount of cost sharing that they will have based on their decision making, there is an opportunity perhaps for patients to choose lower cost facilities. Now, even as I'm saying this out loud, my first concern and worry is making sure that outcomes are the same. And so I, first and foremost, care about complication rates for surgery and things of that nature. But there are state level programs that have shown that we can have both. It can be a dominant solution. So I encourage states to especially have the flexibility to accommodate variations in state level health care markets, the states is really where these databases belong. And they should take it the next step further to make them interpretable, inclusive of all cost. And I encourage states and federally to work together to say if we're getting a colonoscopy, that includes services A, B, C, and D. So when patients are comparing, they're actually comparing apples to apples. Evidence-based standardized quality metrics incorporated into these cost models will help us at least keep thinking about getting to this ultimate goal of value. And it's like hard not to plug when we're talking about cost and everything is this concept of value. And making sure that no matter what structure we choose to show people cost to have it impact their out-of-pocket cost sharing, those services as we have deemed in the evidence to be high value, the screening lung CT, the colonoscopy, really should be at a minimal cost sharing for patients, no matter what sort of structure that we have. No, that makes perfect sense. One of the things that jumped out here, if you actually have data that using an APCD increase the number of patients moving to lower priced facilities from here, you mentioned from 68% up to 90%, the first thing that would occur to me is that that might actually end up driving down prices from competition, which is something that has never been a successful strategy in medical care for some reason. Absolutely. The specific program I'm talking about from California is called CalPERS. And it's the government 1.3 million state employee programs. And really, the premise of that program is so interesting because it's the assumption that we can never really decrease the cost of care unless individual consumers are aware of the prices and have some sort of input into their cost sharing and decision making. Oh, yeah. This is everybody is looking for ways to reduce costs. And when you see success like this, you'd think people would jump all over this. You'd think even hospitals and health systems would want to market that they have lower costs procedures to get more business. It's just very interesting that this is flying so under the radar. Absolutely. And I do think, though, that there are more and more states actually jumping on board. So I'm hopeful in the next five, 10 years that as the real discussion of the value and value based care continue, this will really, I hope, will become more common. And Dr. Kircher, thanks so much for joining me on the podcast. Thank you for allowing me to discuss the paper. Until next time, thank you for listening to this Journal of Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JOP's podcasts are just one of ASCO's many podcast programs. You can find all recordings at podcast.asco.org. And you can also find the full text of Dr. Kircher's paper online at ascopubs.org/journal/jop in August, 2019. This is Dr. Nathan Pennell for the Journal of Oncology Practice signing off.

Dr. Nathan Pennell and Dr. Jennifer Ligibel discuss weight management and physical activity programs for patients with cancer. TRANSCRIPT: Hello, and welcome to the ASCO Journal of Oncology Practice podcast. This is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. I'm sure everyone who listens to this podcast is aware that obesity and lack of physical activity are major health problems in the USA, and they contribute to multiple medical conditions such as heart disease, diabetes. But how much do patients and oncologists know about how obesity and lack of physical activity impact cancer incidence or treatment or outcomes? And how do physicians manage these issues in their practice? With me today to discuss this issue is Dr. Jennifer Ligibel, associate professor at Harvard Medical School and medical oncologist at the Dana-Farber Cancer Institute, where she also serves as director of the Leonard P. Zakim Center for Integrative Therapies and Healthy Living. We'll be discussing her paper, "Oncologists' Attitudes and Practice of Addressing Diet, Physical Activity and Weight Management with Cancer Patients, Findings of an American Society of Clinical Oncology Survey of the Oncology Workforce." Welcome, Dr. Ligibel, and thanks for joining me today. Thank you so much for having me. So just to set the stage for our listeners, how big of a problem is obesity and physical inactivity among cancer patients? Is this something that is generally mirroring the larger problem we see in America, or is there anything different about our cancer patients? Well, we know that obesity and inactivity are risk factors for developing a number of different malignancies. The International Agency for Research in Cancer and the World Cancer Research Fund have both analyzed observational data linking obesity, inactivity, poor dietary quality to the risk of developing malignancy, and have demonstrated really consistent evidence that there is at least 13 different malignancies where obesity, in particular, increases the risk of developing the malignancy. So if you think about the fact that obesity and inactivity are pretty prevalent in the United States, in general, and that these factors also increase the risk of developing malignancy, we find that an even higher proportion of cancer survivors are obese and inactive as compared to the general US population. We also know that treatment that patients get for some malignancies can contribute to weight gain, and also can contribute to inactivity. So you put all of these factors together, and a very large proportion of cancer survivors are at risk for obesity, inactivity, poor dietary quality, or all of those factors together. I mean, the number that you and your co-authors mention is that almost 1/3 of cancer survivors are obese. That seems like a huge number. So clearly a major problem. Yes, that's true. And that number has increased significantly over the last decade. So I know that obesity contributes to cancer risk. But is there data that even treatment of cancer can be impacted by these issues? Yes. So we know that obesity has an impact on treatment-related outcomes and, likely, on the risk of recurrence and mortality in many different diseases. Breast cancer has been the best studied, where we know that women who are obese when they're diagnosed with breast cancer actually have a 35% higher risk of dying from breast cancer compared to women who are of normal weight when they were diagnosed with breast cancer. Similar data are emerging in other malignancies. Colorectal cancer, there has been a strong link with obesity and cancer outcomes. Prostate cancer, gynecologic cancers, there's emerging data as well. So we know that these factors can impact the risk of recurrence and mortality. But there's also evidence that suggests that people who have excess adiposity, have metabolic complications of obesity, are at higher risk of complications like poor wound healing after surgery. They're at higher risk of lymphedema and some malignancies. They may be at higher risk of things like peripheral neuropathy related to chemotherapy. So there are a lot of poor outcomes associated with body weight in cancer patients. Now, I know even dosing of chemotherapy, I believe, obese patients are at risk for under-dosing because people are afraid to give them proper weight-based dosing. So lots of reasons to pay attention to this issue. Is there data, though, that changing that-- intervening with helping patients lose weight or patients at risk losing weight, or increasing their physical activity-- mitigates these risks? That is a great question, and one that will hopefully be answered within the next few years through a number of large-scale, ongoing phase III trials that are looking at the impact of weight loss, increased physical activity, better dietary quality on cancer recurrence and mortality. We don't have data from randomized trials, at this point, looking at the impact of lifestyle change after diagnosis on outcomes. But we do have a lot of observational data that suggest that individuals who are physically active are at lower risk of recurrence in malignancies like breast cancer, colon, and prostate cancer. And we do also have a lot of information from randomized trials that are smaller in scale that demonstrate that losing weight, exercising more has an impact on shorter-term outcomes, like quality of life, cancer-related and treatment-related side effects like fatigue, neuropathy, joint pain. So we know there are benefits of lifestyle change after cancer diagnosis, but we're still awaiting these large-scale trials that will show us whether changing these behaviors actually reduces the risk of recurrence and mortality. So already enough evidence that it's important that we address it, but hopefully, we'll have more convincing evidence soon. Can you take us through the ASCO survey? What was the background to doing the survey, and what did it try to assess? So in 2014, ASCO launched an obesity initiative that really sought to educate the oncology workforce about the connections between obesity and related factors in both cancer risk and outcomes, and to provide tools and resources to help oncologists talk to their patients about physical activity, weight management during and after cancer treatment. There was also a part of the initiative that focused on research and advocacy. We were interested, given that 2014 was a number of years ago, to look at what were the current attitudes of oncology providers toward these topics? What was their practice? Were they talking about weight? Were they talking about physical activity and diet with their patients? And what did they perceive as barriers to really implementing behavior change after cancer diagnosis? And so we designed a survey that would be delivered to individuals that were currently seeing oncology patients. And they could be physicians, they could be nurse practitioners, they could be dietitians or anyone that was currently working with oncology patients and was an ASCO member. And then we asked them questions about their practice, about the attention that they paid to these topics, about what they felt got in the way. And then thinking more broadly about how important did oncology providers think that these topics were in the scope of their practice. Why don't we just jump right into the results? So what were the results from the survey? So first of all, we found that the people that filled out our survey were pretty typical for the general ASCO membership. So about 2/3 of the people that filled out the survey were based in the US. The other 1/3 were international. We did have a higher proportion of medical oncologists, partly because this was limited to people that were actively seeing patients. We had a nice balance of private practice and academic centers, and we had individuals that were treating all different kinds of cancer. So we were happy with the population that filled the survey out as being fairly representative of oncology providers in the US and more broadly. We found, when we asked the providers what were their perspectives on issues related to obesity and cancer, that there was a very strong agreement that obesity impacts treatment outcomes in cancer patients. And in fact, more than 90% of the survey respondents strongly agreed or agreed with that statement, which we were very excited to see. There was also high agreement with addressing a patient's weight should be a standard part of cancer care. And most of their respondents felt that it was the responsibility of the treating physician to recommend healthy diet, regular activity, weight management for patients in whom that was relevant. But there was much less agreement that the oncology workforce felt that they were prepared to be either delivering those interventions or that they had enough information or enough training to really feel comfortable in their skills to help patients start to make these changes. So I thought that was very important that there was high agreement that these things were important, but also a feeling of there needed to be other parts of the health care team that could help patients once these issues were identified in really helping them to make the changes that needed to after diagnosis. We then asked providers about what they were doing now, and we found that the vast majority of providers that completed the survey indicated that they were asking patients about their physical activity patterns, about their diets. They were assessing patients' weights. And this was both during and after cancer treatment. There was a much lower proportion of survey respondents that were actually making referrals to dietitians, to weight management services for their patients. So although there was a lot of discussion and there was an assessment, there wasn't necessarily the next step, which was helping patients actually incorporate these changes through a referral to a skilled provider. And then, the last piece was looking at barriers. And I think that this was something that we were actually a little bit surprised about some of the responses. The last part of the survey focused on looking at the respondents' perceptions of barriers. What did oncology providers feel like was getting in the way of patients changing their diets, exercising more, losing weight when it was relevant? We found that, not surprisingly, lack of time for counseling was something that many providers noted, lack of available resources. So even if you identified that a patient wanted to lose weight or meet with a dietitian, there wasn't necessarily someone that was available. Lack of training or expertise on the part of the oncology provider was also noted. We also found that the majority of participants felt that patients' resistance to behavioral interventions was also a large barrier to helping people make these changes. And this really led us to think start thinking about, well, what is the patient's perception? And I think that's something that we did not cover in this survey, but that is really critical. Because if we find that oncologists are talking about these topics and are trying to reinforce the importance, but patients aren't hearing that or aren't making these changes, then we're really not accomplishing what we want to. So I think from this survey, we now can see what oncologists feel is important and what they're doing in their practices. And we need to figure out, what are the patients hearing and what is the result of the advice that the providers are giving to patients? Yeah, that really is an interesting and kind of a surprising piece. So the first part resonates with me. So I certainly address, you know, in my patients that are in follow-up and survivorship, exercise and trying to maintain a healthy weight. And I also feel that I'm not super comfortable with trying to intervene in that myself, but rather try to suggest that they look for SilverSneakers or some sort of local exercise gym or other opportunities or, perhaps, refer them to a dietitian. But I don't know that I have a perception that the patients wouldn't welcome that advice or that they might be resistant. Is there any plan to try to get an assessment of cancer patients' attitudes on this? So this is something that we are planning at this time. We are trying to develop a survey and partner with some patient advocacy groups to really better understand what the patients' perceptions of these topics are. There is not much currently in the literature, but there have been some assessments. There was a large study that was done in the UK that looked at patients with colorectal cancer and the attention that was paid on the part of their provider to exercise. And if patients remembered hearing about exercise, they were much more likely to do it. So I think that something that we really need to better tease out is, what is the patients' receptivity to this type of information? And are the suggestions that oncologists are making enough to get patients, on their own, to seek out a program? Or do we really need to try to educate providers about effective ways of making referrals? I think the reality is that we also need more programs that patients can be referred to. And something that I think is a real need within the oncology space is programs that help people lose weight that are able to help people become more active, and recognizing some of the limitations that many patients have as a result of their therapy. Things like lymphedema, things like neuropathy, that can be barriers. How can we manage those in oncology patients to help them successfully achieve these behavior changes? And this is, I think, such a great topic because patients really care about interventions that they can do themselves to help their cancer care and their health. And there's so much out there, in terms of complementary therapies and whatnot. But we have real data on things like diet and exercise, and I think more attention being paid to this within cancer centers would really be welcomed by patients. I think so too. You know, we, right now here at Dana-Farber, are leading a trial called the Breast Cancer Weight Loss Trial that's a phase III study looking at the impact of a weight loss intervention on recurrence in women who are overweight or obese when they're diagnosed with breast cancer. And when we started this study, we weren't sure what the uptake would be. It's a very different type of model. But we've enrolled now more than 2,000 patients in less than three years. So there's definitely a very, very significant interest in this topic amongst patients. There's a similar trial going on in ovarian cancer that just enrolled 1,000 patients with a disease that's much less common than breast cancer over just a few years. So I think that the interest on the part of patients in this topic is large and we want to be able to provide them with evidence-based recommendations. There's a lot of stuff out there that's not so evidence-based, especially about diet, and I think that, as oncology providers, we really owe it to our patients to get them the best information that we have about things that they can do to help improve their outcomes and to make themselves feel better during and after their cancer treatment. And we're very lucky to work at institutions like the Dana-Farber Cancer Institute or here at the Cleveland Clinic, where we've actually got a lot of resources devoted to these efforts. But what can people who work at smaller institutions, or really don't have a lot of infrastructure for this, where can they access data or suggestions on how they can counsel patients or help their patients address problems with obesity and lack of physical activity? Is this something that ASCO can help with? So as part of the ASCO Obesity Initiative, we developed toolkits for oncology providers and for patients about the role of weight management and physical activity in cancer. And so those are available at cancer.net. They can be downloaded. You can give them to your patients to start a conversation about the importance of these topics in oncology care. The American Cancer Society also has diet and exercise guidelines for cancer survivors that oncologists can use as a guideline. The American College of Sports Medicine also has a website where they have oncology-trained exercise professionals in different communities. So if a patient wants to work with a trainer that has an understanding of the complications of cancer treatment and the side effects that patients have, that's another good resource. The other thing that is available in many communities is the Livestrong at the YMCA program, which is a free exercise program that's offered for cancer survivors. This is offered now in more than 700 YMCAs across the country. It's a 12-week program that includes both aerobic exercise and strength training. And this is a resource that I send a lot of patients to, and that is available to people not everywhere, but increasingly more places. So that's another good resource for oncologists and for patients across the US. Well, that's fantastic. So good, I'm glad we got to plug that on the podcast. And Dr. Ligibel, thanks so much for talking to me today. Thank you. And I also want to thank all of our listeners out there who joined us for this podcast. The full text of the paper will be available online at ASCOpubs.org/journal/JOP in June 2019. This is Dr. Nate Pennell, for the Journal of Oncology Practice, signing off.

Dr. Nathan Pennell Highlights Key Poster Presentations in Lung Cancer from ASCO's Annual Meeting.  

Dr. Nathan Pennell and author Dr. Thomas W. LeBlanc discuss how open notes have become a routine part of the patient experience, and why physicians might want to elicit and address concerns that arise from notes. Read the related article "Open Oncology Notes: A Qualitative Study of Oncology Patients’ Experiences Reading Their Cancer Care Notes" on JOP

by Dr. Nathan Pennell and Dr. Michael Neuss Related Article: 2017 ASCO Quality Care Symposium: Nurturing a New and Growing Community of Practitioners

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

Dr. Nathan Pennell, Cleveland Clinic, describes treatment of NSCLC patients with HER2 mutations using agents such as Gilotrif or Herceptin.

Dr. Nathan Pennell, Cleveland Clinic, describes treatment of NSCLC patients with HER2 mutations using agents such as Gilotrif or Herceptin.

Dr. Nathan Pennell, Cleveland Clinic, describes treatment of NSCLC patients with HER2 mutations using agents such as Gilotrif or Herceptin.

Dr. Nathan Pennell, Cleveland Clinic, discusses acquired resistance to Xalkori in ALK-positive patients, and second generation inhibitors designed to overcome that resistance, such as Zykadia and alectinib.

Dr. Nathan Pennell, Cleveland Clinic, discusses acquired resistance to Xalkori in ALK-positive patients, and second generation inhibitors designed to overcome that resistance, such as Zykadia and alectinib.

Dr. Nathan Pennell, Cleveland Clinic, discusses acquired resistance to Xalkori in ALK-positive patients, and second generation inhibitors designed to overcome that resistance, such as Zykadia and alectinib.

Dr. Nathan Pennell, Cleveland Clinic, describes other options for treatment of acquired resistance, including chemotherapy, ablation with SBRT and a combination of Gilotrif and Erbitux.

Dr. Nathan Pennell, Cleveland Clinic, discusses the concept of acquired resistance and new agents designed to address it, including Rociletinib and Merelitinib.

Dr. Nathan Pennell, Cleveland Clinic, describes other options for treatment of acquired resistance, including chemotherapy, ablation with SBRT and a combination of Gilotrif and Erbitux.

Dr. Nathan Pennell, Cleveland Clinic, discusses the concept of acquired resistance and new agents designed to address it, including Rociletinib and Merelitinib.

Dr. Nathan Pennell, Cleveland Clinic, describes other options for treatment of acquired resistance, including chemotherapy, ablation with SBRT and a combination of Gilotrif and Erbitux.

Dr. Nathan Pennell, Cleveland Clinic, discusses the concept of acquired resistance and new agents designed to address it, including Rociletinib and Merelitinib.

Dr. Nathan Pennell, Cleveland Clinic, reviews the available trial evidence for the use of targeted therapies in the post-operative/adjuvant setting.

Dr. Nathan Pennell, Cleveland Clinic, reviews the available trial evidence for the use of targeted therapies in the post-operative/adjuvant setting.

Dr. Nathan Pennell, Cleveland Clinic, reviews the available trial evidence for the use of targeted therapies in the post-operative/adjuvant setting.

In this podcast, Dr. Michael Thompson discusses his article, “Using Social Media to Learn and Communicate: It Is Not About the Tweet” with Dr. Nathan Pennell. Cancer Research News

Dr. Nathan Pennell discusses ALCHEMIST, an NCI-sponsored clinical trial looking at whether targeted post-op (adjuvant) therapy for patients with a driver mutation such as EGFR mutation or ALK rearrangement improves survival. http://bit.ly/NCIALCHEMIST

Dr. Nathan Pennell discusses ALCHEMIST, an NCI-sponsored clinical trial looking at whether targeted post-op (adjuvant) therapy for patients with a driver mutation such as EGFR mutation or ALK rearrangement improves survival. http://bit.ly/NCIALCHEMIST

Dr. Nathan Pennell discusses ALCHEMIST, an NCI-sponsored clinical trial looking at whether targeted post-op (adjuvant) therapy for patients with a driver mutation such as EGFR mutation or ALK rearrangement improves survival. http://bit.ly/NCIALCHEMIST

Nathan Pennell, MD, PhD, ASCO Educational Book Associate Editor, discusses the importance of communication between oncologists and their patients in low-resource areas with Matjaz Zwitter, MD, PhD.

by Robert S. Miller, MD. Dr. Nathan Pennell discusses some of the interesting obstacles he encountered when trying to prescribe crizotinib for 3 patients with ALK positive non-small cell lung cancer in the first few weeks following FDA approval in 2011.

Q&A Session following webinar with Dr. Nathan Pennell, medical oncologist and lung cancer expert at the Cleveland Clinic Foundation, on the use of molecular markers such as EGFR, KRAS, ERCC-1, EML4-ALK, and others in NSCLC.

Q&A Session following webinar with Dr. Nathan Pennell, medical oncologist and lung cancer expert at the Cleveland Clinic Foundation, on the use of molecular markers such as EGFR, KRAS, ERCC-1, EML4-ALK, and others in NSCLC.

Dr. Nathan Pennell, medical oncologist and lung cancer expert at the Cleveland Clinic Foundation, reviews the current evidence and future directions for use of molecular markers such as EGFR, KRAS, ERCC-1, EML4-ALK, and others in NSCLC.

Dr. Nathan Pennell, medical oncologist and lung cancer expert at the Cleveland Clinic Foundation, reviews the current evidence and future directions for use of molecular markers such as EGFR, KRAS, ERCC-1, EML4-ALK, and others in NSCLC.