Podcasts about Pennell

Tonight, we'll read the chapter “On Soup” from The Feasts of Autolycus by Elizabeth Robins Pennell, in which Pennell draws from her experiences as a food critic and essayist to explore the role of soup in culinary culture. Snoozecast first read this back in 2020. An American writer who lived much of her life in Europe, Pennell was known for her travel writing and gastronomic studies, often blending personal observations with cultural critique. Her perspective reflects a deep familiarity with both English and French cuisines, informed by her broader interest in art and domestic life. — read by 'V' — Sign up for Snoozecast+ to get expanded, ad-free access by going to snoozecast.com/plus! Learn more about your ad choices. Visit megaphone.fm/adchoices

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  

Aspiring honorary Irishman, Richard Pennell, joins us on this episode to reminisce about four golf trips he undertook to Ireland over the past 12 months. The North Coast & Donegal featured heavily and rightly so. The intrepid traveller also found time to schedule two whistle stop visits to County Mayo on the very Wild Atlantic Way, while also visiting a smattering of what the Dublin area has to offer from a golfing perspective. It amounted to a links overload which left Richard energised and plotting an imminent return. We hope the pod may give you some ideas as to where you might travel to in 2025, however, word of warning it might also make you a little envious that Richard passes these visits off as 'work'..... Either way, many thanks for tuning in, we hope you enjoy our chat! One of the last few copies of Richard's first book Grass Routes can be purchased by following this link (https://pitchmarks.bigcartel.com/product/grass-routes-by-richard-pennell) The Links Diary (https://www.thelinksdiary.com/no-10) Richard has written some great pieces on his @pitchmarks substack account and elsewhere. Please find a few links below to musings on some of his travels around Ireland: County Louth - currently a blank piece of paper.... he has promised us one, just as soon as inspiration arrives Royal Dublin - a work in progress, early 2025 methinks #71 - Portmarnock (https://pitchmarks.substack.com/p/pitchmarks-71-3rd-november-2024-very) #50 - Ballyliffin (https://pitchmarks.substack.com/p/pitchmarks-50-16th-june-2024-the) The North Coast (https://golftoday.co.uk/on-the-causeway-coast/) - an Article that appeared in Golf Today Episode music used under license from Epidemic Sound Special Guest: Richard Pennell.

Love the show? Have any thoughts? Click here to let us know!Step into the shadows of Delaware's haunted past in this chilling episode. First, Kenzie explores the Woodburn Mansion, a historic estate that serves as the governor's residence—and a hotspot for paranormal activity. From ghostly figures to unexplained phenomena, she'll uncover the eerie legends tied to this stately home. Then, Lauren delves into the disturbing case of Steven Brian Pennell, Delaware's only known serial killer. Known as the “Route 40 Killer,” Pennell's heinous crimes terrorized the state and left a legacy of fear. Join us as we weave together the supernatural and the sinister, unraveling Delaware's dark and mysterious tales.--Follow us on Social Media and find out how to support A Scary State by clicking on our Link Tree: https://instabio.cc/4050223uxWQAl--Have a scary tale or listener story of your own? Send us an email to ascarystatepodcast@gmail.com! We can't wait to read it!--Thinking of starting a podcast? Thinking about using Buzzsprout for that? Well use our link to let Buzzsprout know we sent you and get a $20 Amazon gift card if you sign up for a paid plan!https://www.buzzsprout.com/?referrer_id=1722892--Works cited!https://docs.google.com/document/d/1yta4QOa3v1nS3V-vOcYPNx3xSgv_GckdFcZj6FBt8zg/edit?usp=sharing --Intro and outro music thanks to Kevin MacLeod. You can visit his site here: http://incompetech.com/. Which is where we found our music!

Send us a textOn today's Zero Limits Podcast I chat with Jamie Pennell New Zealand Special Air Service and author of Serviceman J: The Untold Story of an NZSAS SoldierJamie Pennell spent 22 years in the New Zealand Defence Force, with 18 years in the NZ SAS.On 28 June 2011, a group of nine gunmen and suicide bombers attacked the Inter-Continental Hotel, Kabul. The attack and an ensuing five-hour siege left at least 21 people dead, including all nine attackers. Responsibility was claimed by the Taliban. Jamie's SAS patrol led the clearance of the hotel encountering many taliban fighters. Subsequently he was awarded New Zealand's second highest military honour by showing outstanding gallantry in the face of danger.During his time in the SAS, he also fought alongside Willie Apiata and was there when his actions led to him being awarded his Victoria Cross.After living the military Jamie's decision to write a book was sparked by encouragement from peers and family, as well as a personal tragedy. The death of our comrade, Steve Askin, motivated James to share his story. He began writing a tribute for Steve's family, which ultimately led him to expand his writing into a full book.Serviceman J: The Untold Story of an NZSAS Soldier

Chatting a top tip from a somatic vocal coach to use in daily life; why the voice is can be so under-rated; the voice & trauma; and fostering a new sense of resilience. Find Eleanor HERE Find the free Shamanic Reiki UK Community HERE Find the wait-list for the Shamanic Reiki Pathway Spring 25 HERE You'll find me most @shamanicreikiuk on IG

Today the lads caught up with Jamie Pennell to discuss his new book; Serviceman J. A gripping memoir by a former NZSAS commander on serving in Afghanistan over five deployments and operating at the edge of his limits In 2011, following the Taliban seige on Kabul's Intercontinental Hotel, an SAS soldier identified only as Serviceman J was awarded New Zealand's second highest military honour by showing outstanding gallantry in the face of danger.  After twenty-two years in the New Zealand SAS, ex-commander Jamie Pennell is now ready to tell his story. Get his book here https://bit.ly/3V1HGbZ  Enjoy.

Piraten, die had je natuurlijk in de Caribische Zee. Grote piraten? Zwartbaard, dat soort namen: intimiderende, Britse mannen. Maar de grootste piratenleider aller tijden was een vrouw. Ze was de rijkste, de slimste, en ze was Chinees. Ze werd de koningin van een schaduwrijk in het zuiden van China, met een eigen economie, een leger dat de grote naties deed bibberen, en met regels die tegen alle heersende normen in gingen.

In this episode, James talks with Josh Pennell. He and James discuss his work at Prosper Advisory, including the firm's accounting and financial planning services, his approach to networking and client acquisition, his expertise in providing financial advice during divorce and separation, and his experience of writing and publishing a book. Josh Pennell LinkedIn: https://www.linkedin.com/in/thefamilyfinanceguy/ Prosper Advisory Website: https://www.prosperadvisory.com.au/ What Parent's Want Book: https://www.amazon.com/What-Parents-Want-financial-happiness/dp/1781337012 moneyGPS. Discover the digital advice platform that will future proof your business: https://ensombl.com/go/20240919 Join the Ensombl platform: App Store: http://www.ensombl.com/apple Google Play: http://www.ensombl.com/google Desktop: https://www.ensombl.com/ General Disclaimer – https://www.ensombl.com/disclaimer/

Former SAS commander Jamie Pennell recounts his experiences in Afghanistan in his memoir, Serviceman J, detailing life in one of the world's elite military forces and the transition to civilian life afterwards.

In 2011, following the Taliban siege on Kabul's Intercontinental Hotel, an SAS soldier identified only as Serviceman J was awarded New Zealand's second highest military honour by showing outstanding gallantry in the face of danger. After eighteen years in the New Zealand SAS, ex-commander Jamie Pennell is now ready to tell his story - his new book Serviceman J The untold story of an NZSAS soldier is out nowSee omnystudio.com/listener for privacy information.

Jamie Pennell had an esteemed 20-year career as a solder and leader inside the NZ SAS.He was sent on four deployments to Afghanistan and in 2011, he was part of the unit which responded to the Taliban's Intercontinental Hotel siege. For his bravery in helping save many lives that day - he was awarded the New Zealand Gallantry Star, the country's second-highest military honour. In this episode Jamie shares his story about what really happened, he talks about the unique culture of resilience and camaraderie within the NZSAS, and the subsequent alienation this can create when soldiers return to civilian life. We hear of touring with Willie Apiata and what happened the day Willie won his Vic Cross, the brutal reality of SAS selection and some of the most eye raising stories from war zones. But this ep is so much more than ‘war stories': in the second half Jamie reflects on what hes seen in men's mental health, grief, and the struggles of reconnecting with his family.  Jamie is now an advocate for rewiring the neural pathways to overcome negative thought patterns. After leaving the Defence Force, he gained his master's in International Security, and trained high performance athletes to reach their goals and He now teaches Learning in the Outdoors to students at Dilworth School. This podcats tackles some serious themes and there are mentions of suicide. It may not be suitable for all listeners.If you, or anyone listening to the podcast - finds this subject challenging, please stop now. And remember, help is available from a range of organisations. There's a list of them in the podcast episode description. We're also like to tell you about the business we've built. If you'd like to hire one of our incredible guests to speak at or MC your event, check out our epic lineup at B2Bspeakers.co.nz and get in touch. This episode is brought to you by TAB, download the new app today and get your bet on! 1737, Need to talk? Free call or text 1737 to talk to a trained counsellor, 24 hours. Anxiety New Zealand 0800 ANXIETY (0800 269 4389) Depression.org.nz 0800 111 757 or text 4202 I Am Hope offers a range of services, with a particular focus on young people. Lifeline 0800 543 354 Mental Health Foundation 09 623 4812, click here to access its free resource and information service. Rural Support Trust 0800 787 254 Samaritans 0800 726 666 Suicide Crisis Helpline 0508 828 865 (0508 TAUTOKO) thelowdown.co.nz Web chat, email chat or free text 5626 What's Up 0800 942 8787 (for 5 to 18-year-olds). Phone counselling available Monday-Friday, noon-11pm and weekends, 3pm-11pm. Online chat is available 3pm-10pm daily. Yellow Brick Road 0800 732 825 Youthline 0800 376 633, free text 234, email talk@youthline.co.nz, or find online chat and other support options here. If it is an emergency, click here to find the number for your local crisis assessment team. In a life-threatening situation, call 111. See omnystudio.com/listener for privacy information.

I'm thrilled to share with you all a sit down with my good friend, Jamie Pennell. Jamie is a former member of the New Zealand Special Air Service (NZSAS), one of the many heroes from the hostage rescue operation in Kabul in 2011 and the author of a gripping new book about his military journey- Serviceman J: The Untold Story of an NZSAS Soldier. We delve into not only Jamie's military experiences, but also his transition to civilian life, family and how he met his wife Alia, and his motivations for writing a book about his journey.
 Jamies's decision to write a book was sparked by encouragement from peers and family, as well as a personal tragedy. The death of our comrade, Steve Askin, motivated James to share his story. He began writing a tribute for Steve's family, which ultimately led him to expand his writing into a full book. Jamie's book offers a raw and authentic look into the life of an NZSAS operator. He shares the gruelling selection process, intense training, and high-stakes operations. His stories highlight the physical and mental toll of serving in special forces.
 In a gripping recount of the Kabul Intercontinental Hotel siege, Jamie Pennell delves into the harrowing details of the operation that unfolded over ten intense hours. The siege began when a group of heavily armed terrorists stormed the hotel, taking numerous hostages and creating a chaotic and perilous environment.  Jamie describes the initial moments of the attack, highlighting the confusion and urgency that gripped both the hostages and the responding forces. The terrorists, equipped with automatic weapons and explosives, had meticulously planned their assault, aiming to maximise casualties and create a high-profile crisis. Jamie emphasises the critical importance of clear communication and coordination among the various responding units, including local Afghan forces and international special operations teams. He details the tactical decisions made in real-time, such as the strategic placement of snipers and the careful breaching of rooms to minimise harm to hostages.  The operation required not only physical bravery but also psychological resilience, as the rescuers had to navigate booby traps and potential suicide vests worn by the terrorists. Jamie's account underscores the complexity of urban combat and the necessity of maintaining composure under extreme pressure to ensure the safety of innocent lives. Jamie recounts the painstaking efforts to gather real-time information and adapt strategies accordingly.  Jamie's detailed narrative provides a vivid portrayal of the bravery and professionalism exhibited by the special forces, shedding light on the often unseen and under-appreciated complexities of Special Forces operations.

Jamie's book chronicles his journey through the rigorous selection process, intense training, and operational experiences in the NZSAS. He provides a realistic portrayal of what aspiring special forces candidates can expect, emphasizing the physical and mental toll of the training and the operational challenges faced during his 18 years in the regiment. This episode of the "Straight Talk Mind and Muscle Podcast" provides a candid and insightful look into Jamie's journey from a member of the NZSAS to a fulfilling civilian life. Through personal anecdotes and practical advice, James inspires listeners to embrace change, cultivate self-awareness, and seek support as they navigate their own transitions. His experiences serve as a testament to the resilience and dedication of those who serve in elite military units, offering valuable lessons for anyone facing challenges in their own lives. You can find Jamie at Linkedin - https://www.linkedin.com/in/jamie-p-189b71123/ And his book at Bookstore in NZ And on Kindle, Audible and Amazon  AMAZON - https://www.amazon.com.au/Serviceman-Untold-Story-NZSAS-Soldier/dp/1775542386 AUDIBLE - https://rb.gy/kn4hr6 I am Damian Porter , Former NZ Special Forces Operator, Subject Matter Expert from www.hownottodieguy.com  and www.eatwellmovewell.net And you are listening to my STRAIGHT TALK MIND AND MUSCLE PODCAST sponsored by www.mystait.com  - the ultimate daily formula for optimum hormone health, stress management, energy and performance.   100% natural and clinically proven ingredients, it provides everything you need to raise your game, in a convenient gut-friendly capsule. 

 And the Mason Survival Protocol    - https://www.carnivoreretreat.com/post/masonsurvival-protocol-carnivore-retreat

Links for my former shows are here-


 WATCH on YouTube- https://www.youtube.com/playlist?list=PLpt-Zy1jciVn7cWB0B-y5WATyzrzfwucZ LISTEN on:  spotify: https://open.spotify.com/show/1rlAGRXCwLIJfQCQ5B3PYB?si=UmgsMBFkRfelCAm1E4Pd3Q Itunes - https://podcasts.apple.com/us/podcast/straight-talk-mind-and-muscle-podcast/id1315986446?mt=2 


  
Amazon https://music.amazon.com/podcasts/5bce2d31-a171-4e83-bada-d1384c877e76   Subscribe for more amazing tips, interviews and wisdom from phenomenal guests -------  #SAS #SpecialForces #Teamwork #MilitaryHistory #SASTraining #Leadership #Transition #Adaptability #LifeAfterService  #MentalResilience #QuickDecisionMaking #PersonalDrive #Integrity #Discipline #MilitaryEthics

A highly-decorated former NZSAS commander has opened up about the Kiwi unit's military operations in a new memoir. Serviceman J details Jamie Pennell's recruitment story and training journey - and lifts the lid on the NZSAS's Afghanistan operations, including the deadly Kabul hotel siege. Pennell says the selection process to join the unit was a difficult one - mentally, physically and spiritually.  "It's very brutal - and that's by design. Operations are quite difficult, so we have to replicate that in our selection process." LISTEN ABOVESee omnystudio.com/listener for privacy information.

Join the Waste No Day! Facebook group: https://bit.ly/3xbqEj0 Follow Waste No Day on YouTube: https://bit.ly/3xlDLhD Lawrence Castillo is the President and Operating Partner of Brody Pennell Heating & Air Conditioning, Los Angeles' most successful HVAC company three years counting.  In this episode, we talked about technician training, service programs, client communication...

In this episode of MPR, we talk with Michael Pennell from Pythons in a Pear Tree about his approach to breeding Dwarf Burmese pythons.  Lucas Lee fills in for Owen on this one. Check out what Michael Pennell has going on: Pythons in a Pear TreeMPR Network SocialsFB: https://www.facebook.com/MoreliaPythonRadioIG: https://www.instagram.com/mpr_network/YouTube: https://www.youtube.com/channel/UCtrEaKcyN8KvC3pqaiYc0RQMORELIA CENTRAL Website: https://www.moreliapythonradio.netEmail: Info@moreliapythonradio.comMPR Support Cold-blooded CafeWe have an affiliate linkhttps://www.coldbloodedcafe.com/Cold Blooded CaffeineWe have an affiliate linkhttps://coldbloodedcaffeine.com/?ref=9wLRgXGdMerch store: https://teespring.com/stores/mprnetworkPatreon: https://www.patreon.com/moreliapythonradio ★ Support this podcast on Patreon ★

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

Meet Barbara Pennell JaynesIn 2013, Barbara founded Positively-Funded. She has engaged with manufacturers, facilitating their strategic growth planning: beta testing, opening new markets, product launches, and creating key industry partnerships. Highlights00:00 Travel Stories and Favorite Destinations03:28 Introducing Barbara Pennell Jaynes04:56 Business Development vs. Traditional Marketing06:04 The Importance of Real-World Feedback08:44 Beta Testing and Storytelling in Manufacturing12:08 The Value of Manufacturing Facility Tours14:14 LinkedIn Strategies and Weird Facts21:23 Conclusion and Contact InformationConnect with Barbara!LinkedInwww.positively-funded.combarbara@positively-funded.com Facebook(303)993-7124Connect with the broads!Connect with Lori on LinkedIn and visit www.keystoneclick.com for your strategic digital marketing needs! Connect with Kris on LinkedIn and visit www.genalpha.com for OEM and aftermarket digital solutions!Connect with Erin on LinkedIn!

Send us a Text Message.This week, Amanda and Lauren head back to the Most Notorious list, this time to talk about Delaware's only serial killer, Steven Brian Pennell.Sources:All That's Interesting: "The Disturbing Crimes Of Steven Brian Pennell, The Only Serial Killer In Delaware History" by Neil PatmoreDelaware Today: "Route 40 Serial Killer Remains an Enigma After Convicted 30 Years Ago" by Delaware Today EditorsWHYY NPR: "Steven Pennell: A mystery man 25 years later" by Nichelle PolstonThe True Crime Database: "#0092 Route 40 Killer: The Delaware Serial Murders" by NucleusMurderpedia: "Steven Brian Pennell"WikipediaSupport us!Drink Moment | Moment Botanical WaterDrink your meditation. Use code MOSTWANTEDAMANDA at checkout!Kind CottonConsciously-sourced, inclusive, impactful, kind clothes. Use code AMOSTWANTEDPOD at checkout!Devon + LangLife changing underwear. Use code MOSTWANTEDAMANDA at checkout!Disclaimer: This post contains affiliate links. If you make a purchase, I may receive a commission at no extra cost to you.

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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 

Recorded 5-16-2024 on OMEGAMAN "Tips from a Shepherd - Part Three" / Ralph Poupart and Larry Pennell / Omegaman Episode 10961  

Recorded 5-9-2024 on OMEGAMAN

"Tips from a Shepherd - Part One" / Ralph Poupart and Larry Pennell / Omegaman Episode 10927 Recorded 5-2-2024 on OMEGAMAN omegamanradio.com  

Stephen and Jim welcome English writer Richard Pennell to the pod to discuss his book Grass Routes.

Overtime With William Patteson HR 2 3.25.24: Max Pennell Joins! by Fanrun Radio

Richard Pennel joined us to talk about his rediscovery of the love for the game - extracted from episode 136If you've enjoyed this episode, please leave us a review on Apple Podcasts or Spotify!You can follow us along below @cookiejargolf Instagram / Facebook / Twitter / YouTube / Website

Overtime With William Patteson HR 2 Podcast 1.11.24: "Max Pennell Joins!" by Fanrun Radio

2023 was a wild year for Dr. Matt Pennell. He opened a new chiropractic location, built a team, welcomed a baby into the world, and grew his business 100%.This week, he's talking with Jacob about 2023 and the lessons & goals he is taking into 2024.

This is a Kahok special edition recorded in the heart of Collinsville at the Old Herald Brewery and Distillery. The first guest is the man who founded the Old Herald, Derik Reiser. Reiser shares his passion for distilling and "bringing something cool" to the downtown Collinsville area. Next up, Kahok Athletic Director Clay Smith discusses all the great energy surrounding Purple Nation and the special nature of guiding the sports programs in his hometown. Then, Head Football Coach Colton Rhodes and quarterback Darren Pennell join the show to accept their MESPY Awards for 7A Team and Individual Player of the Year. Rhodes describes his leadership philosophy, and Pennell, a McKendree commit, talks about making the change from WR to QB just one month before the season. Then, the top tennis player on the Kahok squad, Carter Marlin, stops by to talk about the challenge of playing #1, his goals for the future, and his musical background. Marlin is followed by the three senior leaders on the Collinsville Boys Basketball Team: Nick Horras, Zach Chambers, and Jamorie Wysinger. The 3 hoop stars discuss their team's undefeated start (12-0), the strength of their squad, playing for Coach Lee, the upcoming Holiday Classic Tournament, and their lofty goals for the remainder of the season. Finally, Boys Hoops Coach Darin Lee is joined by his daughter Dani, a tennis player at CHS, who just wrapped up her career on the courts. Coach talks about the style of his team and watching his daughter play tennis; Dani describes her emotions watching her dad's teams play along with her plans for the future.

Having had some time away lately, Leighton & Eddie catch up for a chat and amongst other things - talk about Golf in South African and Tampa. Leighton then sits down with Richard Pennell.  Richard has been in the industry for some time, both on and off thne course having worked at severalk clubs through the Surrey area, including Secretary at Woking Golf Club.  After a sabbatical, Richard rediscovered his love for Golf but also reignitied a passion for writing through his substack blog.  This has even culminated in a book.  Leighton & Richard also talk about some of the challenges of management and looking after yourself.  A really deep thinker, Richard is always a fascinating listen. https://pitchmarks.substack.com/ https://pitchmarks.bigcartel.com/product/grass-routes-by-richard-pennell    

In this episode I walk with illustrator Ethan Pennell, creator of the Dartmoor Folklore Map.  Ethan shares strange tales of phantom monks, spectral woodland, a bleeding cottage, pixies and much more, that he has captured on his brilliant Dartmoor Folklore map.Plus, Ethan shares the creative inspiration for his map and his family's account of a truly enchanting fairy encounter that you won't want to miss! We met at Newbridge car park, on Dartmoor. and walked along the river Dart, passing over Deeper Marsh, where the pixies dance and onto Buckland Bridge where we took the gate into Blackadon nature reserve and then climbed up from there to Blackadon Tor, where we had lunch before returning to New Bridge.  Whilst at Blackadon Tor I captured the sound of the church bells chiming in the background.  However, on reviewing the recording. the bells seem to be distorted into creepy music box style tune. Could this be the tricksy pixies? Let me know what you think! Ethan Pennell links:www.ethanpennell.comEtsy:  Crowmancrowcreations - Etsy UKIG:  @crowmancrow  Ethan Pennell (@crowmancrow) | Instagram profileSupport the Podcast on my Faery Whisperer Buy Me A Coffee Page See Show Notes on my podcast blog www.twitter.com/FaeryWhispering Faery Whispering Facebook group The Faery Whisperer YouTube Channel

We're thrilled to host Lawrence Castillo, the dynamic President of Brody Pennell Heating & Air Conditioning. Based in the bustling city of Los Angeles, CA, Lawrence has emerged as a vanguard in the residential HVAC and plumbing sector, propelling companies to unparalleled revenue heights on the West Coast.We dive deep into Lawrence's captivating journey in the trades. Discover how he climbed the ranks to become a top-tier operator in the industry and the mastermind behind Brody Pennell's recognition as the BEST Heating and Air Conditioning company by Los Angeles Times readers for two consecutive years, 2021 and 2022.We discussed: How To Create A Successful Business ModelHiring Employees That Fit With The BusinessGetting Employees On Board With Business AcquisitionsNuances of the HVAC Industry Between Canada and The United StatesCreating A Memorable ExperienceJoin us for an inspiring session filled with industry insights, leadership advice, and a behind-the-scenes look at what makes a top HVAC company tick in one of America's most competitive markets.Find Lawrence :On The Web: https://brodypennell.com/E-mail: lawrence@brodypennell.comLinkedin: https://www.linkedin.com/in/lacastillo/Facebook: https://www.facebook.com/BrodyPennellYouTube: https://www.youtube.com/c/BrodyPennellLosAngelesJoin Our Group: https://www.facebook.com/groups/hvacrevealedPresented By On Purpose Media: https://www.onpurposemedia.ca/For HVAC Internet Marketing reach out to us at info@onpurposemedia.ca or 888-428-0662Sponsored By: Chiirp: https://chiirp.com/hssrReal Time Marketing: https://realtime360.io/

One Big Family has a Spotify Playlist called New Music Friday: Indie-Christian. HERE is a link to the playlist. Each week we will feature some new track(s) released that week and hear from the artists. This week's featured artists and tracks: Crafted Child + Crafted Choir > Closer Walk Dan Joseph > How To Say Anna Palfreeman + Joseph Pennell > Alone - Joe's Version Ro CV + Kelsey J. > You Are My Fortress (Blessed Assurance) Christian Singleton + Daniel Yates > I Just Want To - accoustic This episode is presented to you by One Big Family. Follow this LINK to the website for OBF. Visual Worship Project Feature Happy New Music Friday!! :)

In Part 2 of our investigation into Freemasonry, we discuss and expose rituals and false teachings of Freemasonry that oppose biblical Christianity. We examine some of its history and explain The Masonic Lodge's emphasis on oaths, symbols, and good works, occult influences, and we contrast these philosophies with the Biblical worldview.

Overtime HR 1 Podcast 10/31/23: "MAX OUT YOUR WINNINGS with Max Pennell by Fanrun Radio

Jay W. Pennell has been a part of the NASCAR industry for over fifteen years. His career path has taken him from that of an independent journalist, to social and digital marketing, to team public relations, and to NASCAR gaming. Jay has written for outlets including FOX Sports, NASCAR.com, Playboy, and Athlon Sports, and was one of NASCAR's first citizen journalists. He also worked with Richard Childress Racing (RCR), handling public relations, content creation, and partnership management. Jay also served as the General Manager of the eNASCAR Heat Pro League, later moving to Brand Manager, NASCAR and INDYCAR with Motorsport Games. His new book is titled Start Your Engines, from Sports Publishing, contains 34 chapters describing different inaugural accomplishments that have taken place throughout NASCAR history.

Per listener request, we're talking about Steven Brian Pennell, infamously known as the Route 40 Killer. In the early 1980s, Pennell terrorized Delaware, abducting and brutally murdering multiple women. In this episode, we'll delve into the disturbing details of his crimes, his methods, and the relentless pursuit by law enforcement to bring him to justice.   And don't forget to check out Cosmic Green Candles for all of your fall-scented needs cosmicgreencandles.com Use code CrimeCulture for 10% off your order!   Email: crimeculturepod@gmail.com Website: crimeculturepodcast.tumblr.com Instagram: @crimeculturepodcast Twitter: @CrimeCulturePod Facebook: @crimeculturepodcast And join our Patreon! (All other links can be found on our website and linktree in our social media bios!) Hosts: Hayley Langan and Kaitlin Mahar Theme Song Composer: Michael Quick Mix Engineer: Elliot Leach We'll see you next Tuesday! xx

Overtime HR 1 Podcast 10/18/23: "MAX OUT YOUR WINNINGS with Max Pennell" by Fanrun Radio

Overtime HR 2 Podcast 10/18/23: "Pro Talk with William Patteson and Max Pennell" by Fanrun Radio

Overtime HR 1 Podcast 10/5/23: "Max Out Your Winnings with Max Pennell" by Fanrun Radio

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

When we spoke to Richard Pennell in February last year his Stymied blog was starting to gain traction. 18 months late he is now a published author his book, Grass Routes, a collection of essays taken from the blog combined with some new material. Pennell's writing focuses not on birdies and bogeys but on golf's more cerebral and emotional joys, the way the game touches people beyond being just a recreation. Links mentioend on this episode: The Kids Golf Podcast Patreon (https://www.patreon.com/KidsGolfPodcast) page and on BuyMeACoffee.com (https://www.buymeacoffee.com/kidsgolfpodcast) or send Rod Morri a DM on Twitter (https://twitter.com/Rod_Morri) Buy 'Grass Routes' here (https://pitchmarks.bigcartel.com) Follow Richard's Substack 'Pitchmarks' here (https://pitchmarks.substack.com) Angus and Grace Go Golfing website (https://www.angusandgracegogolfing.com) and Instagram (https://www.instagram.com/angusandgracegogolfing/)

Special anouncements: Sounder x Cookie Jar Retro Day @ West Byfleet 19th October: https://cookiejargolf.com/cookie-jar-retro-day-west-byfleet/Richard's new book now on sale: 'Grass Routes' available here: https://pitchmarks.bigcartel.com/product/grass-routes-by-richard-pennellRichard returns to the podcast to guide us through this wonderful Course Diaries episode about West Byfleet. A course which had not been on our radars until he started work there in recent years, and spent hours waxing lyrical about its architectural merits and fascinating history that it shares with New Zealand golf club.  In this episode we talk about the inception of Bleakdown Golf Club as it was known for its first years when Locke-King handed the parcel of estate land over to the locals for the use of golf, Muir Ferguson who ran this little slither of Surrey with an iron fist, Cuthbert Butchart, Braid and of course JF Abercromby. It's a wonderful course, and hopefully this episode will show you why you shouldn't overlook West Byfleet the ext time you're visiting somewhere new in Surrey. For more on Richard, his substack page is a constant stream of great musings on the game and can be accessed free of charge on the link hereIf you've enjoyed this episode, please consider leaving us a review on Apple Podcasts or Spotify!You can follow us along below @cookiejargolf Instagram / Facebook / Twitter / YouTube / Website

Eric Pennell host of “Busting Balls” podcast is back on the den previously episode 1, 3, 24, 44, 100 and 148 links below.  We talk about crazy people at open mics, dealing with your lady, doing mushrooms with a transgender and RIP Gary Coleman!    Support The Lobo Den Podcast by joining the Patreon with bonus content and more: https://www.patreon.com/theloboden   The views expressed on the podcast are of The Lobo Den Podcast and do not reflect the views and positions of anyone ever.   I'm back on Roast Battle this Thursday 6/1 Anthony Fuentes episode 89. 6/2 Racine at Evelyns Main and 6/17 Delavan featurning for Chris Barnes.  Link for the tickets in my Link Tree below.    YouTube: https://youtu.be/1R2WewPdGTA   Instagram: https://www.instagram.com/ericpennellcomedy/ https://www.instagram.com/lobo9110/ https://www.instagram.com/thelobodenpodcast/   Best Group on Facebook: https://www.facebook.com/groups/830054804387858   TikTok (aka CCP weaponized social media app): https://www.tiktok.com/@theloboden   Twitter: https://twitter.com/lobodenpodcast https://twitter.com/lobo9110   Donate: https://www.paypal.me/thelobodenpodcast   Links: https://linktr.ee/theloboden   Episode 1 The Lobo Den Podcast - Eric Pennell & Ryan Andrews at Cigars & Stripes https://youtu.be/MX36A8V8sRU   Episode 3 The Lobo Den Podcast - Eric Pennell & Todd Glover at Cigars & Stripes https://youtu.be/4QUJfw1kfys   Episode 24 The Lobo Den Podcast Eric Pennell, Greg Bartusiak & Ramiro Lynch "Arrested Dadvelopment" https://youtu.be/_3uO1syZNm4   Episode 44 The Lobo Den Podcast Eric Pennell "Polish Car Accident" https://youtu.be/U2sHBGm4xmw   Episode 100 The Lobo Den Podcast Jessica & Eric Pennell "We're Having a Baby!" https://youtu.be/ZmSfMLM1Uu4     Episode 148 The Lobo Den Podcast Eric Pennell "Pill Popping Momma's" https://youtu.be/5YwAO5NW_Yc      

Welcome to yet another week! In today's episode Zig takes a deep dive into another Doctor with the 6th Doctor: Colin Baker. Meanwhile Geoffrey tells the tale of Steven Brian Pennell.For your 30 day free Audible Trial go to: Audibletrial.com/nerderyandmurderyFor 10% off with BetterHelp go to: betterhelp.com/nerderyandmurderySupport the show

By early July 1988, he had already tortured, mutilated, and killed two women. Police were stumped until they sent in one of their own undercover. And while his wife and children slept, 30-year-old Steven Brian Pennell took the bait. Learn more about your ad choices. Visit podcastchoices.com/adchoices

With fear of confrontation and anxiety about disappointing loved ones, Steven Brian Pennell pent up his rage. He'd often drive along Highway 40 in Delaware to clear his head. After killing his first hitchhiker, he realized there was only one way to satisfy his desires. Learn more about your ad choices. Visit podcastchoices.com/adchoices

We discuss and clarify teachings of Freemasonry that oppose biblical Christianity, examine some of its roots, explain why it is in fact a religion, The Lodge's emphasis on rituals, symbols, and good works, and we contrast its beliefs and practices with the Biblical worldview.