POPULARITY
Send us a textJoin us for our second discussion with Professor Alison Birtle on metastatic prostate cancer.This time we look at mCRPC. What are our choices after first line therapy.We discuss;-PARPi and BRCA testing-Docetaxel re-challenge-Cabazitaxel-Patient SupportThis is a real tour de force by Alison.We hope you enjoy.John & Mike
Rick Greene, MD, discusses with Lorenzo Ferri, MD, PhD, the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy. Dr. Ferri is author of, "Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network." Dr. Ferri is Professor of Surgery and Oncology, McGill University; David S. Mulder Chair of Surgery Head, Division of Thoracic and Upper Gastrointestinal Surgery, McGill University Health Centre; and, Director, Upper G.I. Cancer Program, McGill University, Montreal, Canada.
Chest pains and severe fatigue drove Valerie David to seek medical attention, which led to a diagnosis of Stage 3B Cell Diffuse Large Cell Non-Hodgkin's Lymphoma. A chemotherapy regimen helped her achieve survivorship. However, years later, she discovered a lump under her armpit. After getting it checked out, she was diagnosed with Stage 2 Invasive Lobular Carcinoma, a form of breast cancer. Again, aided by a chemotherapy regimen, Valerie survived this diagnosis, but not long after that, she was diagnosed with Stage 4 metastatic breast cancer. Despite the staging, Valerie was prescribed a less aggressive form of chemotherapy, and survived. Inspired by her cancer journey, she written and starred in an award-winning one-woman play, “The Pink Hulk,” seen through the United States and in Europe.
“I can't stress enough how often I get questions about, ‘Is this the paclitaxel doing this? Is this the docetaxel doing this?' And coming up with strategies to kind of help get our patients through with supportive care is important. It's a really big opportunity for pharmacists and our nurses to really provide it and help our patients get through and show the knowledge that we have and to help them,” Dane Fritzsche, PharmD, BCOP, oncology informatics pharmacist at the Fred Hutchinson Cancer Center and University of Washington Medicine in Seattle, WA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a discussion about the plant alkaloid drug class. You can earn free NCPD contact hours after listening to this episode and completing the evaluation linked below. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.75 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at myoutcomes.ons.org by February 16, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to plant alkaloids. Episode Notes Complete this evaluation for free NCPD. Oncology Nursing Podcast series: Pharmacology 101 Cancer Symptom Management Basics Oncologic Emergencies 101 ONS courses: ONS/ONCC Chemotherapy Immunotherapy Administration Certificate™ ONS Fundamentals of Chemotherapy and Immunotherapy Administration™ ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook Clinical Journal of Oncology Nursing articles: Vincristine Minibag Administration: A Quality Improvement Project to Minimize Medical Errors Taxane-Induced Peripheral Neuropathy: Objective and Subjective Comparison Between Paclitaxel and Docetaxel in Patients With Breast Cancer Liposomal Irinotecan: Nursing Considerations in an Outpatient Cancer Center Extremity Cooling: A Synthesis of Cryotherapy Interventions to Reduce Peripheral Neuropathy and Nail Changes From Taxane-Based Chemotherapy ONS Huddle Card: Plant Alkaloids ONS Symptom Interventions and Guidelines ONS Voice article: Chemo-Induced Peripheral Neuropathy May Have a Link With Vitamin D Deficiency Hematology/Oncology Pharmacy Association patient education IV Cancer Treatment Education Sheets ChemoCare To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “An alkaloid is an organic compound, so think carbon-based ring structure. The only thing special about alkaloid is that it has to contain at least one nitrogen atom.” TS 1:43 “Plant alkaloids are just alkaloids derived from plants itself, so think like the roots, stems, leaves, bark, and things like that. Each of these agents we'll discuss today are unique, but broadly speaking, all of them are extracted, at least when they were first discovered, from a plant source. And they are typically biosynthesized by these plants for defensive purposes.” TS 2:01 “Broadly speaking, [plant alkaloids] are cell cycle–specific agents. They do, depending on the compound, impact different parts of the cell cycle. Topoisomerase inhibitors is an example, so think irinotecan, which is a topoisomerase I inhibitor. There's topoisomerase II inhibitors, like etoposide being a good example. These impact the S phase in your cell cycle, so the synthesis of the DNA. Topoisomerase kind of helps unwind DNA and stabilize that as it's being replicated.” TS 3:36 “Again, these plant alkaloids kind of fall into your typical chemotherapy side effects, so we're thinking rapidly dividing cells. Our bone marrow—so is it lowering our red blood cells, our white blood cells, our platelets? And then it can also affect our GI [gastrointestinal] tract, whether it causes diarrhea in some cases; in some other cases, it can actually cause the other way and cause severe constipation. And then a lot of these agents do lead to hair loss.” TS 5:28 “The last thing I want to touch on with paclitaxel is neuropathy, or your pins and needles, tingling in the tips of your hands and toes. That is the most common one. That's a sensory neuropathy. But we also can see motor neuropathies with this agent, where the patients start to struggle with their fine motor skills, like buttoning shirts, using pencils, things like that. This is a cumulative dose effect with paclitaxel. So if patients are on multiple, multiple, multiple cycles, we definitely start to ask, you know, how that's going. And we expect at some point this is going to become an issue as therapy continues.” TS 9:26 “The last class we are going to touch on for more agent specifics is our vinca alkaloids. I think the biggest takeaway and something that was just kind of hammered into my brain during residency and during pharmacy school is that these agents should never be in a syringe, and that's because they are fatal if they're accidentally given intrathecally.” TS 11:41 Neuropathy-wise, it's challenging, and it's something that throughout my whole career with patient care, it constantly comes up. And there's really no one great solution to it. There's many different guidelines out there and papers out there that recommend some stepwise approaches. At the end of the day, too, we have to think about, what are our goals with our patients? How much is this limiting? TS 16:44 “Unfortunately, these hypersensitivity reactions are somewhat routine because we have lots of patients getting these medications, and they're not uncommon, like you said. It's really just that team-based approach. And since they are routine, we're all pretty comfortable at handling these.” TS 22:51 “I've always appreciated just our team-based collaboration. My clinical nurse coordinators that I worked with very closely are all kind of our number-one go-to for our patients. So I mentioned anything that's happening, any questions you have, reach out to your doctors or nurse here. They know everything. And when they don't know everything, then they know who to reach out to.” TS 28:59 “You have to remember a lot of these agents have very agent-specific side effects. So don't just think you know them all just because you know it's a plant alkaloid. Remember and do your due diligence and dive into each drug.” TS 33:27
Drs Sandhya Srinivas and Tanya B. Dorff discuss metastatic hormone-sensitive prostate cancer, which patients are the best candidates for doublets vs triplets, and how we pick these patients. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988737). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Prostate Cancer https://emedicine.medscape.com/article/1967731-overview Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment https://pubmed.ncbi.nlm.nih.gov/37220335/ Triplet or Doublet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Updated Network Meta-Analysis Stratified by Disease Volume https://pubmed.ncbi.nlm.nih.gov/37055323/ PSMA PET in Imaging Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35155262/ Risks and Cancer Associations of Metachronous and Synchronous Multiple Primary Cancers: a 25-Year Retrospective Study https://pubmed.ncbi.nlm.nih.gov/34556087/ The Promise of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer: Going Beneath the Surface With Molecular Imaging https://pubmed.ncbi.nlm.nih.gov/35058322/ Gleason Score https://www.ncbi.nlm.nih.gov/books/NBK553178/ Luteinizing Hormone-Releasing Hormone (LHRH) Receptor Agonists Vs Antagonists: a Matter of the Receptors? https://pubmed.ncbi.nlm.nih.gov/23418666/ The Role of CYP17A1 in Prostate Cancer Development: Structure, Function, Mechanism of Action, Genetic Variations and Its Inhibition https://pubmed.ncbi.nlm.nih.gov/29372682/ Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial https://pubmed.ncbi.nlm.nih.gov/29384722/ Abiraterone for Prostate Cancer Not Previously Treated With Hormone Therapy https://pubmed.ncbi.nlm.nih.gov/28578639/ Abiraterone Plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/28578607/ Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP https://pubmed.ncbi.nlm.nih.gov/34928708/ Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35179323/ Abiraterone Plus Prednisone Added to Androgen Deprivation Therapy and Docetaxel in De Novo Metastatic Castration-Sensitive Prostate Cancer (PEACE-1): a Multicentre, Open-Label, Randomised, Phase 3 Study With a 2 × 2 Factorial Design https://pubmed.ncbi.nlm.nih.gov/35405085/
Cisplatin is the mainstay for concurrent chemoradiotherapy in Locally Advanced Head and Neck Cancers. What happens to that significant group of patients who cannot have cisplatin? Michael and Josh focus on this challenging subgroup of patients. Can docetaxel be used as an alternative? This week, they debut a small but significant segment of our humble podcast called "Spotlight", where we dive deep into a single potentially practice-changing trial. Enjoy!Links to studies discussed in this episode (subscription may be required):Docetaxel as a radiosensitiser: https://ascopubs.org/doi/abs/10.1200/jco.22.00980#:~:text=We%20found%20that%20the%20use,of%20life%20of%20the%20patients.For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.
A new research paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC).” Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy. This new retrospective study, by researchers Hazem I. Assi, Maroun Bou Zerdan, Mohammad Hodroj, Makram Khoury, Nour Sabiha Naji, Ghid Amhaz, Reine Abou Zeidane, and Fadi El Karak from the American University of Beirut Medical Center and Hotel Dieu de France University Hospital, was based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians' clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. “The main aim [of this study] was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC.” A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, their study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months. “New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.” DOI - https://doi.org/10.18632/oncotarget.28444 Correspondence to - Fadi El Karak - Felkarak@yahoo.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28444 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - chemotherapy, immunotherapy, non-small cell lung cancer About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Guest host Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss several crucial studies that will be presented at the 2023 ASCO Genitourinary Cancers Symposium, including ARASENS, TRITON3, and others in prostate cancer, as well as novel therapies in mRCC and urothelial carcinoma. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome Dr. Jeanny Aragon-Ching, a medical oncologist and the clinical program director of the Genitourinary Cancers Program at the Inova Schar Cancer Institute in Virginia. Today we will be discussing key abstracts in genitourinary oncology that will be featured at the 2023 ASCO Genitourinary Cancers Symposium. Our full disclosures are available in the show notes, and disclosures for all guests on the podcast can be found on our transcripts at asco.org/podcasts. Jeanny, it is great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal, for having me. Dr. Neeraj Agarwal: So Jeanny, let's begin with Abstract 15 on the update on the ARASENS trial, which Dr. Maha Hussain will present [at the meeting]. In March ‘22, as we know, almost a year ago, the results of the ARASENS trials were published in the New England Journal of Medicine. Darolutamide, which is an AR signaling inhibitor plus androgen deprivation therapy plus docetaxel chemotherapy, significantly reduced the risk of death by 32.5% versus placebo plus ADT plus docetaxel. The effect of triplet therapy, including darolutamide on overall survival, was consistent across prespecified subgroups. However, survival outcomes by disease volume were not reported at the time. Can you please tell us about Abstract 15? Dr. Jeanny Aragon-Ching: Yeah, thank you so much, Neeraj, I would be happy to. So, this new data is actually very crucial for all clinicians. The title of this abstract is “Efficacy and Safety of Darolutamide in Combination with ADT and Docetaxel by Disease Volume and Disease Risk in the Phase 3 ARASENS Study.” So, as a quick reminder, in this trial, patients were randomized 1:1 to the standard dose of darolutamide 600 milligrams twice daily or placebo with ADT and docetaxel in the metastatic hormone-sensitive prostate cancer setting. Now remember, too, high volume disease was defined per the charted criteria, which is visceral metastases and/or four or more bone lesions, of which at least one or more has to be beyond the vertebral column or pelvis. 8And high-risk disease was actually defined per the LATITUDE criteria, which is any two or more of the following three factors: Gleason scores eight or more, bone lesions that are three or more, and the presence of measurable visceral metastases. Of all the 1,305 patients, 77% of them were actually classified as having high-volume disease, and 70% of them had high-risk disease. So, in both of these high-volume and low-volume disease patients, the triplet therapy darolutamide, ADT, and docetaxel actually improved overall survival and hazard ratio was 0.69 and 0.68, respectively. Compared to the placebo and ADT, and docetaxel arm. So overall survival improvement was also significant in patients across all risk, high-risk, or low-risk disease. Dr. Neeraj Agarwal: So, Jeanny, this is great news. So, the main message from this abstract for our audience is that triplet therapy of darolutamide plus docetaxel plus ADT is more efficacious than the doublet of ADT plus docetaxel chemotherapy, regardless of disease volume or risk status. One important caveat I would like to note is that triplet therapy with the darolutamide was not compared with the doublet therapy of ADT plus darolutamide or any androgen receptor signaling inhibitor such as abiraterone or apalutamide or enzalutamide, all of which have shown benefit consistently, regardless of volume status, and in the case of abiraterone, also in the context of high-risk disease setting, as we saw in the LATITUDE trial. Dr. Jeanny Aragon-Ching: Absolutely. I agree with that, Neeraj. Those are important points to consider. Now, moving on to a different setting in prostate cancer across the disease continuum, let's discuss Abstract 18, titled “Rucaparib for Metastatic Castrate-Resistant Prostate Cancer.” This is TRITON3 entering overall survival and efficacy of rucaparib versus docetaxel or second-generation engine pathway inhibitor therapy, which will provide us with some additional data regarding overall survival. Neeraj, based on this new abstract, can you tell us more about TRITON3, which will be presented by Dr. Alan Bryce and colleagues from the Mayo Clinic Arizona? Dr. Neeraj Agarwal: Of course. So TRITON3 is a randomized multicenter open-label phase 3 trial where rucaparib was compared with the physician choice of docetaxel chemotherapy or abiraterone or enzalutamide in those patients who had not received chemotherapy in the metastatic castration-resistant prostate cancer setting, and they had to be progressing on a prior androgen receptor signaling inhibitor in any setting prior. So, they just had to have disease progression either in the hormone-sensitive setting or CRPC setting on one of the AR inhibitors, and they had to have a BRCA1, BRCA2, or ATM alteration. So, in this context, these patients were randomized to rucaparib versus physician's choice of agent, which could again be docetaxel chemotherapy, abiraterone, or enzalutamide. So, OS maturity is 54% in BRCA group and 59% in the intention to treat population. In BRCA1 and BRCA2 populations, radiographic PFS, which was the primary endpoint, was 11.2 months in rucaparib group and 6.4 months in the physician choice arm. In the intention to treat population where you include all patients BRCA plus ATM patients, ATM positive patients. Radiographic PFS was 10 months almost versus 6.4 months with standard of care. And both were statistically significant as well as clinically meaningful improvement in the radiographic progression-free survival with rucaparib over physician's choice of either docetaxel or enzalutamide, or abiraterone. I would like to note that most frequent toxicity which we see with this group of agents is most frequent grade III or more toxicity was anemia, which was present in approximately 24% patients treated with rucaparib. Dr. Jeanny Aragon-Ching: Yeah. This is a really exciting update, Neeraj. What do you think is the key takeaway from this abstract? Dr. Neeraj Agarwal: The key takeaway is that TRITON3 trial met its primary endpoint, and rucaparib significantly improves radiographic progression-free survival in BRCA mutation-positive patients or BRCA ATM-positive patients. Overall survival is still immature, and these results further establish rucaparib as one of the standard of care options in those patients who have metastatic CRPC with prior treatment with the AR signaling inhibitor and who harbor one of the BRCA mutations or BRCA NAT mutations. So, Jeanny, before moving on to the renal cell carcinoma section in this podcast, there is an Abstract in prostate cancer talking about correlation between the source of funding and disparities among patients with advanced prostate cancer. So, I'm referring to that Abstract 40, titled “Source of Funding and Enrollment Disparity in Prostate Cancer Clinical Trials.” I thought this was an interesting abstract. Could you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in Abstract 40, Dr. Riaz and Dr. Bryce, and colleagues actually looked at phase II and III clinical trials that involved prostate cancer patients that reported on patients with age by 65 years, and they got the data from the MEDLINE and Embase databases. Trials recruiting from the United States were considered eligible for analysis by race and ethnicity. So, in terms of race and ethnic enrollment, they found that black patients were significantly underrepresented in the industry's funded trials. Notably, no significant disparity was observed in the US government-funded trials, but Hispanics were also significantly underrepresented in industry-funded clinical trials. However, no significant disparity was seen in terms of older adults overall and by funding sources. Remarkably, Black patients' representation in industry-funded prostate cancer trials has actually decreased over the last three decades. Dr. Neeraj Agarwal: That's concerning. So, what is your key takeaway from this trial, Jeanny? Dr. Jeanny Aragon-Ching: The key message here is that Black and Hispanic men with prostate cancer are significantly less likely to be included in industry-sponsored clinical trials. A bigger concern is that black patients' representation actually continues to decline over time. So these results warrant a really more proactive role by regulatory bodies to ensure that a proportional representation of minorities in the industry trials, which in turn will make these results more applicable to a wider entire population of men with prostate cancer. Dr. Neeraj Agarwal: Thanks, Jeanny. Let's move on to renal cell carcinoma. I saw some innovative research correlating the efficacy of immune checkpoint inhibitors with the time of the day these checkpoint inhibitors were administered. So, interestingly, there were two studies from two different groups of investigators showing very similar results. Please tell us about this innovative research correlating outcomes with immune checkpoint inhibitors with the time of the day these medicines or these drugs were infused into the patients. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. I think they're very exciting and interesting. So there's actually two abstracts, so Abstract 681 and 678, which we, of course, can discuss separately. So, let's probably start first with Abstract 678. Neeraj, do you want to explain to us further about this abstract? Dr. Neeraj Agarwal: Yes. When our center participated in that abstract, which was led by Dr. Nazli Dizman from Yale University, Dr. Dizman and colleagues examined the relationship between the time of the administration of immune checkpoint inhibitors, or ICIs, as we call them, during the time of the day, and outcomes in patients with metastatic renal cell carcinoma. So, I'd like to point out that previously Dr. Qian and colleagues reported an association between the time of day of immunotherapy infusion and survival outcomes in patients with metastatic melanoma. In this study, Dr. Dizman and colleagues, which included our center also, patients with metastatic RCC who received nivolumab with or without ipilimumab– so these patients all received either nivolumab alone or without ipilimumab. And patients who received less than 25% of infusion after 4:30 pm. were assigned to the early-time of infusion group. So, if they have received less than 25% infusion of these immunotherapies after 04:30 pm in the evening, they belong to the early infusion group, and the rest were assigned to the late infusion group. In the univariate analysis, numerically higher objective responses and time to treatment failure were observed in the early infusion group compared to the late infusion group. So, differences were 33% versus 25% in objective responses in early versus late infusion group. If you look at time to treatment failure, 8.3 months versus 4.4 months in early versus late infusion group. In the multivariate models, which took into account the clinical characteristics such as age, gender, line of treatment, IMDC risk category, histological subtypes, there was a trend towards improved outcomes in those who received these infusions with ICIs early in the day. So, Dr. Dizman concluded that larger randomized and controlled investigations are warranted to examine the impact of this chronal modulation, if you will, on the efficacy of immune checkpoint inhibitors in metastatic RCC sets. Dr. Jeanny Aragon-Ching: Yeah, this is very interesting data, Neeraj. And that actually resonates closely with this other abstract by Fernandez Manias and colleagues in Abstract 681. So, in this abstract, the primary outcome was overall survival, but they did look at other secondary endpoints like time on treatment, time to the next treatment, and overall response rates. Now, because of the small number of events, the authors actually focused on just patients who received second-line immune checkpoint inhibitors. And what they did was they looked at patients who received overall more than 20% of their infusions after 04:30 pm, and they found that those who did receive actually fewer infusions had a significantly shorter time on treatment and had a worse overall survival. And similar results were seen when they looked at those who got more than 50% of their dose of checkpoint inhibitors that were administered after 04:30 pm, so interestingly enough, there was a 16% increase in the risk of death for each 10% increment of checkpoint infusion after 04:30 pm. So the key message here is that administration of checkpoint inhibitors after 04:30 pm is associated, unfortunately, with inferior outcomes. Now, these results should, of course, be further considered in the organization overall of the outpatient clinic as it can impact patient survival and outcomes. Dr. Neeraj Agarwal: Very interesting. So similar results from two independent groups of investigators from two different continents obviously made this research area very appealing and pertinent. Ideally, I think these results should be validated prospectively, but that will take time. But investigators who have already lagged multiple phase III trials should explore validating these results in the last phase 3 trials which have already been reported and where the data on the timing of infusion is available. Once validated, I think these results may profoundly influence how we organize, as you said, Jeanny, the outpatient scheduling of these checkpoint therapy infusions compared to those who are not checkpoint inhibitors. I think this is going to have very interesting data overall, no doubt. Before moving onto bladder cancer, I would like to discuss an important abstract related to testicular cancer patients titled “Longitudinal Evaluation of Plasma MicroRNA-371 to Detect Minimal Residual Disease and Early Relapse of Germ Cell Tumors.” Could you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this is a very interesting up-and-coming Abstract, it's number 407, which will be presented by Dr. Lucia Nappi and colleagues. In this study, clinical patients with stage I germ cell tumor with available plasma samples after they underwent radical orchiectomy were all included. So, they looked at sensitivity, specificity, negative, positive predictive values, an area under the curve in predicting tumor recurrence, and they evaluated the microRNA-371, I'll just call it and truncate it as miR-371, and compared the same operating characteristics of current gold standard diagnostic tests. Relapse-free survival was correlated to post-orchiectomy miR-371 status, which could be either positive or negative. So, at a median follow-up of 41 months, 101 patients with clinical stage one germ cell tumor were included. About 35% of them experienced a disease relapse during that time of follow-up. Now, what they found was miR-371 was positive in about 63% of the relapsed patients, and the miR-371 positivity preceded clinically evident disease by a median of about three months. The specificity and positive predictive values were 100%, sensitivity was like 63%, and negative predictive value was 83.5%, so very high. No false positive results were seen. And, the authors reported that the recurrence-free survival of the patients who had positive post-orchiectomy miR-371 was significantly shorter compared to those patients who had a negative biomarker for the miR-371. So, they concluded that the miR-371 sensitivity correlated with the tumor burden, time between tumor relapse, the microRNA testing, and histology. It was notably a little bit more sensitive in non-seminomas compared to those who had seminoma. Dr. Neeraj Agarwal: Interesting findings, indeed. So, Jeanny, what is the take-home message from this abstract? Dr. Jeanny Aragon-Ching: Yeah, so I think the key takeaway is that microRNA-371 seems to be a good test, like a biomarker for predicting disease relapse in patients with early-stage germ cell tumor. So, additionally, its high specificity and positive predictive value in predicting relapse could really be used and utilized to guide adjuvant therapy, selections, and decisions after orchiectomy. Further validation in other studies, such as swab 1823, are currently ongoing or planned to validate its clinical utility. So Neeraj, moving on to bladder cancer, the last abstract I'd like to mention before we wrap up the podcast is Abstract 563, titled “Utility of ctDNA in Predicting Outcome and Pathological Complete Response in Patients with Bladder Cancer as a Guide for Selective Bladder Preservation Strategies.” Neeraj, can you tell us more about this abstract? Dr. Neeraj Agarwal: Sure. So, this study was led by Dr. Lars Dyrskjøt. He and colleagues evaluated the prognostic value of circulating tumor DNA, or ctDNA, in predicting recurrence in a cohort of 68 patients with muscle-invasive bladder cancer who received new adjuvant chemotherapy prior to cystectomy. So ctDNA was analyzed two times at baseline before new adjuvant chemotherapy and then before surgery or before cystectomy. So, patients had ctDNA assessed before neoadjuvant chemotherapy and then before cystectomy after completion of new adjuvant chemotherapy. At baseline, of the 64 patients, around 60% were ctDNA negative, and 40% were positive for ctDNA. So of those patients who were ctDNA negative, 84% achieved pathologic complete response, while in those who tested ctDNA positive, only 35% achieved their pathologic complete response after surgery. Prior to surgery, 84% of patients were ctDNA negative, and 81% achieved pathologic complete response. While none of the ctDNA-positive patients who were positive before surgery and after neoadjuvant chemotherapy, none of them achieved pathologic complete response, which translates into a positive predictive value of 100% and a negative predictive value of 81% for this test. So based on both ctDNA time points, the probability of ctDNA negative patients to achieve a pathologic complete response was significantly higher than ctDNA positive patients. At a median follow-up of 59 months, ctDNA-positive patients without pathologic complete response demonstrated significantly lower recurrence-free survival and overall survival compared to those who were ctDNA negative. So, I want to repeat that, at a longer follow-up, which Dr. Dyrskjøt will be presenting, ctDNA positive patients without pathologic complete response had significantly lower recurrence-free survival and overall survival compared to ctDNA negative patients. Furthermore, ctDNA status at baseline, which is before neoadjuvant chemotherapy and before cystectomy, was a better predictor of recurrence-free survival compared to pathologic complete response, which is a remarkable finding here, although it's a smaller data set. Dr. Jeanny Aragon-Ching: Agree completely, Neeraj. So, I think the importance here, too, is upon prospective validation in larger data sets, we will find that a negative ctDNA test would help in identifying patients who can benefit more from bladder-sparing strategies. Neeraj, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Before I share my final thoughts, Jeanny, I would like to thank you for joining us and sharing your insights. I always find them very valuable. So, thank you so much for taking the time. I would like to wrap up the podcast by saying we are seeing an explosion in the development of novel therapeutic approaches for our patients with genitourinary cancers. At the 2023 ASCO GU meeting, we will have multiple studies with practice-impacting data presented by investigators from around the world. I urge our listeners to come and join us in the meeting not only to celebrate these successes but also to help disseminate these cutting-edge data to practitioners and maximize the benefit for our patients across the globe. I would like to thank our listeners for joining us today. You will find links to the abstracts which we discussed today on the transcript of this episode. Finally, 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. Thank you so much. 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, experiences, 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. Neeraj Agarwal @neerajaimms Dr. Jeanny Aragon-Ching Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma
In this JCO Article Insights episode, Davide Soldato summarizes two articles from the January 10th, 2023 Journal of Clinical Oncology issue: “Low-Intensity Chemotherapy for Early Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial” and “Inflammation and Clinical Decline After Adjuvant Chemotherapy: Results From the Hurria Older Patients Prospective Study .” Both articles report on clinical outcomes of elderly patients treated with chemotherapy for early-stage breast cancer. TRANSCRIPT Davide Soldato: Thank you for joining JCO Article Insights. I'm Davide Soldato. Today I will be providing summaries for two different articles focused on elderly patients treated for early-stage breast cancer. Both articles are reported from the Hurria Older Patients With Breast Cancer Study. This study is also known as the HOPE Study, and it was a multicenter, prospective, study of patients aged 65 years and older treated with current standard (Neo)adjuvant chemotherapy regimens for early-stage breast cancer. The study captured several detailed geriatric clinical and treatment data from 500 patients that were recruited between September 2011 and May 2017 in 16 sites across the United States. The first article is titled ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women'. In this article, Dr. Sedrak and colleagues used data from the HOPE Study to investigate the incidence of chemotherapy administration with low relative dose intensity, associated risk factors, and relationship with survival outcomes. Previous data already showed that the receipt of chemotherapy with a low relative dose intensity is associated with inferior survival outcomes, and the commonly used threshold to define a low relative dose intensity is 85%. And this same threshold was used inside of the study that I am reporting. Elderly patients that are treated with chemotherapy are at higher risk of receiving chemotherapy with low relative dose intensity because of toxicity. However, previous data on the topic was mainly retrospective in nature and reported heterogeneous rates of low relative dose intensity up to 75%. And also, little information was available on risk factors and on the impact on survival outcomes. So, considering the paucity and the quality of the previous data and the potential clinical implication for survival outcomes, results of the HOPE Study are extremely relevant to clinical practice as they provide novel insight on the topic from a prospective multicenter study. In the analysis that was reported in the January issue of JCO, the authors excluded patients with HER-2 positive disease, those receiving nonstandard chemotherapy regimens, and those with upfront chemotherapy dose reduction. The final analytic cohort included 322 patients with a median age of 70 years, 44% with stage II, and 22% with stage III disease. Docetaxel and cyclophosphamide, and anthracycline-based chemotherapy, and this one, either alone or with subsequent paclitaxel, were the most commonly used chemotherapy regimens. Additionally, 85% of patients received a primary prophylaxis with G-CSF. Relative dose intensity was variable in the study. More than half of the patients received full course chemotherapy with 100% relative dose intensity. However, the incidence of low relative dose intensity in the HOPE study was still 21%, thus identifying a subset of patients who received chemotherapy with a suboptimal dose intensity. The rates of low relative dose intensity were higher for patients receiving either anthracycline-based chemotherapy and those with a planned treatment duration over 12 weeks. The authors developed a multivariable logistic regression model with stepwise selection to identify risk factors associated with low relative dose intensity. The results of this analysis showed that an age higher than 76 years, administration of anthracycline and CMF-based regimens, and a physician-rated Karnofsky Performance Status under 90 were associated with higher risk of low relative dose intensity ranging from 3 to 5 times greater compared to reference categories. Then the authors realized another model where they used the previously mentioned three variables, but they also adjusted for relevant clinical characteristics, including age, stage, liver and renal function, and also previous cardiovascular disease. And in this model, the three variables that were observed previously— age, type of chemotherapy, and Karnofsky Performance Status—remained significantly associated with higher risk of receiving chemotherapy with a low relative dose intensity. Finally, the Authors evaluated the association between a low relative dose intensity and survival outcomes, specifically breast cancer-specific mortality, non-breast cancer-specific mortality, and overall survival. Patients who received the chemotherapy with a low relative dose intensity had a significantly lower overall survival, and this association persisted even after excluding patients older than 76 years. A higher risk of both breast cancer and non-breast cancer mortality was observed in patients with low relative dose intensity chemotherapy. However, the number of cause-specific events was too low to obtain statistical significance for both these endpoints. In conclusion, the study by Dr. Sedrak and colleagues provides several relevant information for clinical practice. First, the HOPE study demonstrates that the administration of chemotherapy to elderly patients while maintaining an appropriate relative dose intensity is feasible. However, 1 in 5 patients received chemotherapy with a low relative dose intensity. So the results of this study reinforced the need to identify upfront patients most likely to require dose reduction. And these patients should be proactively supported during the administration of chemotherapy to ensure that appropriate toxicity management can reduce the risk of low relative dose intensity. Second, in the study, the authors observed a significant association between a low relative dose intensity and the CARG and CARG-BC scores. These scores were previously validated to predict chemotherapy toxicity. The presence of this association is important because it suggests that these validated scores can be used routinely in clinical practice to identify patients that might benefit from a comprehensive geriatric assessment to optimize comorbidities treatments and assure optimal delivery of chemotherapy. Finally, longer follow-up will provide the opportunity to establish if the higher mortality that was observed in the HOPE study in patients receiving chemotherapy with a low relative dose intensity is consequent to the low chemotherapy efficacy or to a clinical decline that might be consequent to chemotherapy itself. I will now move to the second article titled ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer'. This article was published by Dr. Ji and colleagues, and it describes a secondary analysis of the HOPE study. In this specific manuscript, the authors wanted to evaluate the potential predictive role of baseline inflammatory biomarkers on the risk of clinical decline after administration of chemotherapy. In the HOPE study, the authors collected information on frailty stages, pre and post-chemotherapy using the Deficit-Accumulation Index (DAI): this is a 50-item scale that evaluates deficits in physical activity of daily living, instrumental activities of daily living, psychosocial status, nutrition, frequency of falls, number of medications, comorbid conditions, social support, and laboratory values. The inflammatory biomarkers that were evaluated in the current study were CRP and IL-6, and their levels were determined on pre-chemotherapy blood specimens. Using the deficit accumulation index score, patients were categorized pre-chemotherapy as being robust, pre-frail, or frail; this is important because previous studies already demonstrated that there is a significant association between this categorization and morbidity and mortality outcomes in older adults. The primary outcome of the study was a chemotherapy-induced clinical decline that was defined as a decline from a robust stage pre-chemotherapy to a pre-frail or frail status after chemotherapy. The overall analytic cohorts included 295 robust women. The median age was 69, 62% of patients had stage II or III disease, median number of comorbidities was 1.9, and mean BMI was 28.5. One in 4 older women included in the study experienced a chemotherapy-induced decline in frailty status, so this means that they transitioned from a robust status pre-chemotherapy to a pre-frail or frail status after chemotherapy. This decline in frailty status was more frequent among patients with a higher BMI, those with more comorbidities, and those with stage II and III disease. Additionally, the patients who experienced chemotherapy-induced decline had higher baseline levels of both IL-6 and CRP. Univariate analysis also showed that patients with high IL-6 and CRP had a threefold higher risk of experiencing chemotherapy-induced decline in frailty stages. This association between higher inflammation and the decline in frailty status remained significant in a multivariable logistic regression analysis that was adjusted for relevant clinical and demographic characteristics, including age, stage, race, education, BMI, breast cancer surgery, anti-inflammatory medication, and number of comorbidities. Specifically, the results of these models showed that patients who had both high CRP and IL-6 at baseline had a threefold higher risk of experiencing a decline in frailty status. So, in conclusion, this study shows a significant association between systemic inflammation and a decline in frailty status in elderly patients receiving chemotherapy for early-stage breast cancer. From a biological perspective, these higher levels of systemic inflammation might be a direct byproduct of a more advanced biological aging following the accumulation of senescent cells. There are several intriguing future perspectives that come from this study. First, if validated in additional cohorts, these findings might lead to higher treatment personalization thanks to the identification of patients at risk of clinical decline based on clinical characteristics but also on systemic inflammation. And these patients could be then proactively supported during chemotherapy to try and reduce the appearance of the clinical decline. Second, we know that inflammation is a potentially targetable pathway, and previous data obtained in breast cancer patients showed the potential of behavioral, exercise, and dietary interventions in modulating systemic inflammation. So, based on this new information, if validated in additional cohorts, future research should then evaluate if this interventions can be used to treat and eventually prevent the decline in frailty status in patients with high baseline systemic inflammation before receiving chemotherapy. This is Davide Soldato in this episode of JCO Article Insights. We discussed two publications: ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results from the Prospective Multicenter HOPE Trial', and the second one, ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults with Breast cancer: Results from the Hurria Older Patients Prospective Study'. Thank you for your attention, and stay tuned for the next episode. 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. Guests' 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. Like, share and subscribe so you never miss an episode and leave a rating or review. Articles Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer Find more articles from the January 10 issue.
Could some Naloxone Products Be Sold Without a Prescription? Find out this and more in today's PVRoundup podcast.
Axel Merseburger describes the results of this randomised trial in Lancet Oncology.
Heute und in den beiden folgenden Episoden wollen wir uns mit dem 74. Kongress der Deutschen Gesellschaft für Urologie in Hamburg befassen. Nach zwei Jahren war es der erste wirkliche Präsenz-Kongress mit rund 6.500 Teilnehmerinnen und Teilnehmern. Man spürte überall die Lust auf Gespräche und persönliche Kontakte. Ein starkes Comeback! : „Wir“ habe ich eben gesagt, denn der heutige Podcast findet zu dritt statt: Aus Lübeck ist Priv.-Doz. Dr. Marie Christine Roesch zugeschaltet. Sie ist Funktionsoberärztin und Co-Leitung Forschungslabor Urologie auf dem Campus Lübeck des Universitätsklinikums Schleswig-Holstein und Medizinische Schriftleiterin von UroForum. Der Dritte im Podcast-Bund ist Dr. Ronny Reimann, Fachredakteur Urologie der Mediengruppe Oberfranken in Kulmbach. Die Themen: 1) Die TITAN-Studie zum Prostatakarzinom .- Subanalyse zum Docetaxel (marie-Christine Roesch 2) Der Berufsverband der Deutschen Urologen - Neustart mit Fehlzündungen (Franz-Günter Runkel) 3) Klimaschutz und Nachhaltigkeit in Klinik und Praxis (Ronny Reimann)
FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)
Listen to a soundcast of the 8/5/2022 FDA approvals of Enhertu (fam-trastuzumab deruxtecan-nxki) for patients unresectable or metastatic HER2-low breast cancer, and Nubeqa (darolutamide) for adult patients with metastatic hormone-sensitive prostate cancer.”
Dr Berchuck discusses the effects of treatment intensification with darolutamide in men with metastatic hormone-sensitive prostate cancer, the significance of the approval of darolutamide plus docetaxel and androgen deprivation therapy, and lingering questions left unanswered by the pivotal ARASENS study.
With a family history of prostate cancer, Max Schlueter wasn't surprised when he was diagnosed. What did come as a surprise was his cancer metastasizing to hip and spine. A treatment regimen combining Lupron and chemotherapy kept the cancer at bay; however, years later, the cancer returned years later attacking the nerve linings of his legs and feet, rendering him a paraplegic. Between determination, his Buddhist faith and a stellar team of physician therapists, Max regained his ability to walk. Now retired, he has returned to an active lifestyle of skiing, kayaking and mountain climbing.
Quelle est la place du Docetaxel dans le CaP métastatique en fonction du VOLUME ?Comment les essais sur l'acétate d'abiraterone ont défini le HAUT RISQUE ? »Quel traitement proposer aux patients à faible volume et/ou métachrones ?Le Dr DARIANE (Hopital européen Georges Pompidou, Paris) répond à toutes vos questions ! L'orateur n'a pas reçu de rémunération pour la réalisation de cet épisode. Cet épisode a été réalisé grâce au soutien institutionnel des laboratoires JANSSEN Certaines données publiées peuvent ne pas avoir été validées par les autorités de santé françaises. La publication de ce contenu est effectuée sous la seule responsabilité de l'éditeur et de son comité scientifique.Musique du générique : Via AudioNetworkResponsable projet AFUF : Dr Benjamin PradèreProduction : La Toile Sur Ecoute Voir Acast.com/privacy pour les informations sur la vie privée et l'opt-out.
In this episode, Daniel W. Lin, MD; Alicia K. Morgans, MD, MPH; and David F. Penson, MD, answer audience questions from a live CCO webinar focused on current best practices and emerging strategies in androgen deprivation therapy, with questions including:How to select between GnRH agonists and antagonists for initial androgen deprivation therapy?How should androgen receptor inhibitors be incorporated into treatment paradigms for nonmetastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer?How should patients with prostate cancer and bone density issues be managed?How should nonmetastatic and metastatic prostate cancer be classified in light of novel imaging modalities, and how does this affect treatment?Presenters:Daniel W. Lin, MDProfessor and Chief of Urologic OncologyDepartment of UrologyUniversity of WashingtonSeattle, WashingtonAlicia K. Morgans, MD, MPHGenitourinary Medical OncologistDana-Farber Cancer InstituteBoston, MassachusettsDavid F. Penson, MDProfessor and ChairDepartment of UrologyVanderbilt University School of MedicineNashville, Tennessee Content based on an online CME program supported by educational grants from Astellas, Bayer HealthCare Pharmaceuticals Inc., Myovant Sciences Ltd, and Pfizer, Inc. Link to full program:https://bit.ly/3iFCis5
In this episode, Chris Parker, MD, and Bertrand Tombal, MD, PhD, discuss the clinical implications of the latest data on radiopharmaceuticals in the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Topics include:Data from the PEACE-3 trial on the effect of bone-protective agents on fracture risk with enzalutamide plus radium-223Efficacy and toxicity of PSMA lutetium plus standard of care in the VISION trialOngoing trials evaluating radionuclides in combination with other agents in metastatic CRPCPresenters:Chris Parker, MDProfessor of Prostate OncologyInstitute of Cancer ResearchClinical OncologistDepartment of Uro-oncologyRoyal Marsden HospitalSutton, Surrey, United KingdomBertrand Tombal, MD, PhDProfessor of UrologyInstitut de Recherche Clinique (IRC)Cliniques universitaires Saint-LucChairmanDepartment of SurgeryCliniques universitaires Saint-LucBrussels, BelgiumLink to full program, including downloadable slides: https://bit.ly/36IEnNE
Interview with Thomas Hatschek, MD, PhD, author of Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer: A Phase 2 Randomized Clinical Trial
Interview with Thomas Hatschek, MD, PhD, author of Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer: A Phase 2 Randomized Clinical Trial
ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's podcast, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2021 Genitourinary Cancers Symposium, and 2021 ASCO Annual Meeting. This episode has been adapted from the recording of a live Cancer.Net webinar, held June 16th, 2021, and led by Dr. Neeraj Agarwal, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Timothy Gilligan. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute. Full disclosures for Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan are available at Cancer.Net. Greg Guthrie: So today, let's introduce our participants. First we have Dr. Neeraj Agarwal of Huntsman Cancer Institute and University of Utah and the Cancer.Net Specialty Editor for Prostate Cancer. Next we have Dr. Petros Grivas from Fred Hutchinson Cancer Research Center and University of Washington. He is the Specialty Editor for Cancer.Net for Bladder Cancer. Next we have Dr. Tian Zhang of Duke Cancer Institute. And she's our Cancer.Net Specialty Editor for Kidney Cancer. And last, we have Dr. Timothy Gilligan. He is with the Cleveland Clinical Taussig Cancer Institute and the Specialty Editor for Testicular Cancer. So to start off, we'll have Dr. Agarwal talking about prostate cancer. Dr. Agarwal: Thank you, Greg. It's such a privilege and honor to be here discussing these studies. So I would like to start with the first study, which was led by Dr. Stephen Freedland, a urologist at the Cedars-Sinai Medical Center in Los Angeles and was co-authored by me, Dr. Dan George, and many others. And here in this study, we present the utilization of therapies, which are associated and known to be associated with very significant, in fact, I would say dramatic improvement in overall survival, as shown by multiple randomized control trials over the period of the last 5 to 6 years. Just to take a step back for the audience, until 2014, standard treatment for metastatic castration-sensitive prostate cancer or newly diagnosed metastatic castration-sensitive prostate cancer used to be androgen deprivation therapy. And combining androgen deprivation therapy with those medications which were approved in the castration-resistant metastatic prostate cancer setting. So basically, using those drugs upfront led to dramatic improvement in overall survival with 33% to 35% reduction in risk of death across those clinical trials. So we actually wanted to look at the real-world utilization, so look at the real-world users of these medications in these patients who are being diagnosed with -- newly diagnosed metastatic prostate cancer in the United States. We also wanted to see how patients who belong to minority populations or racial minority populations, how they are being treated with these medications, which are backed by level 1 evidence. So this was a retrospective analysis of a Medicare database, more than 35,000 patients were included from 2009 to 2018. And we can see here a very representative patient population, predominantly white patients, 11.8% were African American, and 5% were Hispanic. And here are the results. From 2010 to 2014, the use of standard androgen deprivation therapy with bicalutamide, was used in 97% of patients. We did not have trials reporting by that. Let's go to 2015 to 2016. Docetaxel was already approved in this setting now, and we can see some patients received docetaxel, but a small minority of patients received docetaxel. And then let's move to 2018, which is 4 or 5 years after docetaxel data had been presented by Dr. Sweeney in the ASCO plenary session. And abirateron was approved in 2017, and we are still seeing even like almost 2 years after -- we are still seeing the vast majority of patients being treated with standard androgen deprivation therapy or standard deprivation therapy with bicalutamide. So 62% plus 19%, we are talking about almost 80% of patients still not being treated with standard of care treatment, which is androgen deprivation therapy plus docetaxel, or androgen deprivation therapy plus abiraterone at this point of time, and now we have 2 more drugs available, which include enzalutamide and apalutamide in this study. Another interesting thing was if you look at the patients who belong to minority populations, so let's look at African American patients compared to Caucasian patients. The use of intensified therapy was numerically lower. So in Caucasian patients, we are seeing higher use of intensified, as we call them, intensified therapy, or therapies which are considered standard of care, compared to African American men. So overall, the use was lower across the board, but if you look at African American men, the usage was even lower. So this is definitely concerning. I call it alarming, underutilization of life-prolonging therapy in patients who are being diagnosed with newly -- or new diagnosis of metastatic prostate cancer, and we definitely can improve this. We can definitely offer better care to our patients. It is not acceptable in my view to have 30% or less patients receiving standard of care therapies. So with that, I'll go to the next study. Greg Guthrie: Great, thanks. And this study is, “Health-related quality of life and patient-reported outcomes at final analysis of the TITAN study of apalutamide versus placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy.” And you were the presenting author of this, Dr. Agarwal? Dr. Agarwal: Yes, Greg, thank you for giving the opportunity to present this study. And this is basically the continuation of the previous trial. I will not delve into in-depth analysis of these data. I just wanted to show that quality of life is not being impacted adversely by using intensified androgen deprivation therapy, so if you are using these drugs, which improves survival in a very significant fashion, and they are not being used in our patients, as we just saw in the previous study, what could be the reason? Is it the concerns about quality of life or adverse impact on quality of life? If that is the concern, this study, I think, helps refute those concerns. And in this study, which was a large study known as the TITAN trial, which led to approval of apalutamide for patients with hormone-sensitive or castration-sensitive metastatic prostate cancer and showed improved survival and radiographic progression-free and overall survival. We looked at quality of life data as reported by these patients, and these quality-of-life data were assessed by very standardized, validated scales known as FACT-P, or Functional Assessment of Cancer Therapy Prostate scale, or Brief Pain Inventory tool. And there are many other tools. So I will show you the results. And we can see here consistently there was no difference in quality of life as reported by the patients, or I would say any adverse impact on quality of life for these patients in any of these questions. As they were taking these questionnaires. So whether it was physical wellness, emotional wellness, functional well-being, social, or family, we go in and look at fatigue and there was no adverse impact on quality of life. At least from this perspective, we should not be concerned about using these drugs up front in our patients who have newly diagnosed metastatic prostate cancer. Greg Guthrie: Great. And so what does this mean for patients? Dr. Agarwal: From patient perspective, we can see here very clearly that using standardized tools, very validated tools, which have been used in multiple trials in the past, patients are not reporting any adverse impact on their quality of life when being treated with intensified androgen deprivation therapy. In this context, apalutamide. Greg Guthrie: Great. Alright. So let's move on to our next study, which is, “Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer.” The VISION trial. Dr. Agarwal: Thank you. In my view, this is 1 of the most important studies presented in the 2021 ASCO Annual Meeting. This study was a phase 3 study where 7,000 patients were recruited, and they had metastatic castration-resistant prostate cancer and had disease progression on a prior novel hormonal therapy such as enzalutamide or abiraterone and the patients had received a taxane chemotherapy. So at least 1 taxane chemotherapy was required before the trial, and the patient had to have disease progression on a novel hormone therapy. These patients were randomized in 2 to 1 fashion to a novel drug, which is a type of radiation, intravenous radiation, as I would explain to my patients, and this is known as beta radiation. And this is a novel radiotherapy where radiation particle, which is delivering beta radiation particle to the cancer cells, is tagged to a molecule, which binds with the prostate cancer cells. So I'm simplifying it for the sake of our patients. And this particle or this compound was added to standard of care therapy and patients were randomized to standard of care therapy versus standard of care therapy plus this new compound. And standard of care therapy was a novel hormonal therapy or anything which did not include chemotherapy or radium 223, which is another type of radiation particle, but a different kind of particle known as alpha particle. So in this study, radiographic progression-free survival and overall survival were primary endpoints. We can see here that the study met both primary endpoints. There was a significant improvement in radiographic progression-free survival with an almost 5 month, 5.4 months, to be precise, improvement in radiographic progression-free survival, with a 60% reduction in risk of disease progression or death. If you look at overall survival, it was also improved in a significant fashion in patients who received the new compound known as lutetium-PSMA-617, and the median survival was improved by 4 months with an approximately 40% reduction in risk of death. This was a well-tolerated drug overall, and if you look at hybrid side effects, treatment, and emergent side effects, there were 52.7% of patients in the experimental arm, and 38% in the control arm had those treatment-related side effects. So overall, Wwell-tolerated regimen with improved overall survival and radiographic progression. Thank you very much. Greg Guthrie: Thank you, Dr. Agarwal. This is really interesting, and it will be interesting to see if this treatment does change standard of care based on this research. Let's move on to Dr. Grivas and bladder cancer research. Let's see, so Dr. Grivas, your first study is, “Avelumab first-line maintenance for advanced urothelial carcinoma: analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.” And Dr. Grivas was a co-principal investigator in this trial and is senior author of the New England Journal of Medicine publication and co-author of this abstract. Go ahead, Dr. Grivas. Dr. Grivas: Thank you so much, Greg, and thank you to Cancer.Net for the opportunity, and thanks to the audience. We welcome questions. I would like to update the audience today about the data we saw at the ASCO meeting, and I would like to place this data in context, and I would remind the audience the JAVELIN Bladder 100 trial that changed clinical practice was initially presented last year at the ASCO Virtual Meeting 2020 by Professor Powles. And this particular trial tried to answer the following question: does the immunotherapy, especially the PD-L1 inhibitor avelumab, add value in patients who completed chemotherapy in the first-line setting of metastatic urothelial cancer compared to just best supportive care in terms of longer life, in terms of overall survival, and time until the cancer grows or death, progression-free survival? This is important because until this study came about last year, the practice was, in the setting of spread metastatic urothelial cancer, when the chemotherapy stops, was we cannot give it for a long time because of potential side effects. Usually you used to wait until the cancer grows back, it progresses, or grows. So this trial compared this approach, the best supportive care, versus the immunotherapy with avelumab and the best supportive care. This particular trial, so the significant improvement of life expectancy and overall survival as well as progression-free survival, time until progression of the cancer or death, in the patients that received this immunotherapy drug avelumab as a way to maintain or sustain the benefit that is seen with chemotherapy. So we call this a maintenance therapy approach because we tried to maintain or sustain the benefit with chemotherapy. I want to highlight that this was published in the New England Journal of Medicine and the audience can retrieve that from PubMed if one wants to read the manuscript. The bottom line is this trial changed practice, and we can go now to updates. We saw this in this particular meeting, ASCO 2021, and I think the main question was, are there any particular subsets of patients, different categories of patients, who benefit more from the avelumab maintenance approach, or does this benefit all the patients? And we saw at the ASCO meeting, we saw that the benefit with this immunotherapy appears consistent across the board, across different subcategories of groups of patients. And I think that it's important to point out that we looked at patients who had what we call local disease around the bladder, that was invading this area, and the pelvic side wall that was not amenable to surgical rejection and also patients with spread of the cancer in distant sites, what we call metastasis. And we look at patients who had a primary origin in the bladder or higher up in the urinary tract, what we call kidney pelvis, or ureter, and we call this upper urinary tract, versus the lower tract, which is the bladder, and we also look at patients who had metastatic spread in the lymph nodes only or other parts of the body. And with the bottom line, we saw that the benefit with the immunotherapy was consistent across the different groups of patients. So many patients benefit from this treatment, again, with variable degrees, variable magnitude of benefit, but overall, the bottom line is, take home message is if you have clinical factors or other molecular factors, we do not have a reliable, accurate tool to select which patients should go with avelumab, so we offer it nowadays in every patient who has no contraindication to get immunotherapy and has received some disease control. Meaning a response of the cancer or stabilization of the cancer with the chemotherapy phase. So that has real clinical implications, and I encourage the audience to discuss with their oncologist about the optimal roles of immunotherapy with this maintenance setting after chemotherapy when this is controlled with chemotherapy. Just for context here, I want to highlight the options the patients have in clinical practice. And when someone is diagnosed with spread urothelial cancer, they can be offered nowadays avelumab as a maintenance strategy to maintain the benefit of chemotherapy, and the other options include immunotherapy up front, like drugs like pembrolizumab or atezolizumab, and I will come back to that question how to select your treatment in my last slide. And I want to point out these are the options, and obviously clinical trials are always a great option for patients, and they should ask their oncologist about those options. So since I talked about immunotherapy, I want to point out that the ideal chemotherapy is cisplatin-based chemotherapy. Not everybody has enough fitness of the body to tolerate cisplatin. For those patients, we think cisplatin may be too much, we use carboplatin/gemcitabine, and we use avelumab maintenance in that scenario. What about immunotherapy after that? Is there data supporting that use? And the answer is yes. There is some data suggesting that immunotherapy can be an option for some of the patients, and in this particular slide, we update the data from another clinical trial. And I will let Greg, you can read the title of that. Greg Guthrie: Sure, so this study is, “First-line pembrolizumab in cisplatin-ineligible patients with advanced urothelial cancers response and survival results up to 5 years from the KEYNOTE-052 phase 2 study.” Dr. Grivas, you're a co-author on this study. Dr. Grivas: That's right, thank you, Greg. This trial presented longer follow up to see what happened in patients who received the immune checkpoint inhibitor anti-PD called pembrolizumab because they were not fit enough to get cisplatin chemotherapy. Keep in mind this was designed before the previous study I showed you presented the results and included patients who were not fit for cisplatin, but some of them could have been fit for carboplatin. There was no comparison here, everybody received pembrolizumab as a single agent, alone, and in this particular study, we would try to see the degree of shrinkage of the cancer and the overall response rate as well as how long people lived over time. So with longer follow-up, by the way, we published this study in the Lancet Oncology years ago, and we have longer follow-up, and what you see here is a degree of shrinkage of the cancer, what we call overall response rate, was about 29% in what we call all comers, and it was higher size of tumor shrinkage in patients with high PD-L1 expression. PD-L1 is this brake of the immune system, the checkpoint of the immune system and highly expressive measured by particular assay that pembrolizumab works better in those patients. However, some patients even with low PD-L1 measured by this CPS score I put in the slide still might have benefits, so the take-home message here is there is a particular proportion of patients who can benefit from the checkpoint inhibitor pembrolizumab. PD-L1 can be used in that setting to help decide between chemotherapy and immunotherapy. However, we have not compared directly the chemotherapy followed by the available maintenance with immunotherapy up front, so this question is still lingering. However, if the patient has a response shrinkage to pembrolizumab, many of those patients may have a long-lasting response. We tried to figure out with research how can we predict who is going to benefit more from this treatment as a matter of ongoing research. Greg Guthrie: Dr. Grivas, can you really quickly define CPS for our audience? Dr. Grivas: Absolutely. Great question. CPS is a tool we use in the pathology labs to measure the PD-L1 expression. It can be measured by different assessing antibodies, and the pathologists use a score to define if the PD-L1 is high or low. In this particular study, CPS of 10 or higher defines PD-L1 high expression, CPS below 10 defines PD-L1 low expression, and this appears to have some association with a chance of the tumor shrinking with immunotherapy with pembrolizumab. Greg Guthrie: Great. Thanks, Dr. Grivas. So our last study is, “Pembrolizumab versus investigator's choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer: 5-year follow-up from the phase 3 KEYNOTE-045 trial.” Dr. Grivas Very quickly, this study compared immunotherapy, pembrolizumab, the anti-PDL1, compared to chemotherapy with paclitaxel, docetaxel, or vinflunine, the latter one is in Europe, after progression of cancer growth on platinum-based chemotherapy. This was published in the New England Journal of Medicine a few years ago, and pembrolizumab prolonged survival, people lived longer compared to the chemotherapy. And this longer follow-up presented by Dr. Bellmunt and colleagues, showed the sustained results with follow-up, this population of patients had already received cisplatin-based chemotherapy and the cancer progressed, growth, despite that chemo, and in those patients, pembrolizumab appears to produce better results compared to this salvage chemotherapy shown in that slide. And this has implications because immunotherapy can be used in those patients after progression on platinum-based chemotherapy. And just to wrap up here the discussion, I just want to give the options to the patients, see if someone has a new urothelial cancer, options include cisplatin/gemcitabine, or if someone is not fit enough for cisplatin, carboplatin/gemcitabine, and both of those scenarios can be followed by avelumab, and those with shrinking or stable disease, patients who have progression on platinum-based chemotherapy can get pembrolizumab and of course other options available. We can go into another podcast, and I encourage the audience to look and discuss with their oncologist about those options, and the take home message, the clinical trials is what got us here, and I recommend clinical trials to be discussed with your oncologist. Thank you so much, and I'll be happy to take questions. Greg Guthrie: Thanks, Dr. Grivas. So we're going to move on to Dr. Zhang, who is going to talk about kidney cancer. So our first study today is, “Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: a randomized, double-blind, phase III KEYNOTE-564 study.” Dr. Zhang: Thanks, Greg. I'm really excited to be here today and thanks, everyone, for joining. KEYNOTE-564 was presented at the ASCO plenary by our colleague Dr. Toni K. Choueiri, and this is a highly anticipated study in the adjuvant space for kidney cancer and enrolled patients with high-risk clear cell kidney cancer who had undergone either nephrectomy or a metastastectomy, removing their few sites of metastatic disease and treating those patients with either pembrolizumab for up to a year or placebo. And the endpoint was disease-free survival, and enough events had occurred by this ASCO for us to see the primary results. So the overall -- the study was positive. For the primary endpoint, disease-free survival improvement was met with a hazard ratio of 0.68 and the estimated disease-free survival rate at 2 years was 77% for patients treated with pembrolizumab versus 68% for patients treated with placebo. The overall survival favored pembrolizumab, but it was not yet statistically significant, and follow-up will be needed. Overall, we see an improvement in disease-free survival delaying time until recurrence for patients treated with pembrolizumab, and this was the first study in this adjuvant space showing checkpoint inhibition has a role in adjuvant treatment of renal cell carcinoma. Greg Guthrie: Thanks, Dr. Zhang. Our next study is, “Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: results from 42-month follow-up of KEYNOTE-426.” Dr. Zhang: This study, KEYNOTE-426, we are all very familiar with. Pembrolizumab and axitinib has been used for the last 2 years in the first-line treatment of clear cell metastatic kidney cell cancer, and it's a longer-term follow-up, more events and more understanding of what happens to these patients once they're treated in a longer term, so primary endpoints of course of this phase 3 study were progression-free survival and overall survival. When we're looking at this medium duration of follow-up at 42 months, so about 3 and a half years, pembrolizumab and axitinib improved both median overall survival as well as median progression-free survival. We'd point out that the -- at the 3 and a half year mark, the overall survival rate for patients treated with the combination was about 57.5%. And the progression-free survival rate was about 25%, so about a third of patients had not had progression of disease at 3 and a half years. Which is quite meaningful if they can stay on their first-line treatment for that long. The objective response was 60%, and of note, the complete response rate had been updated to about 10%. So there are some patients that do have delayed complete responses. And no new safety signals were observed. So overall, certainly still provides a lot of evidence to treat with pembrolizumab and axitinib for patients in the front-line setting. Greg Guthrie: Great. And our last study here is, “Health-related quality of life analysis from the phase 3 CLEAR trial of lenvatinib plus pembrolizumab or everolimus versus sunitinib for patients with advanced renal cell carcinoma.” Dr. Zhang: This was the phase III trial in first-line treatment of metastatic clear cell kidney cancer that was reported at GU ASCO in February of 2020, and it was a 3-arm randomization to lenvatinib with everolimus in the standard study, and lenvatinib with pembrolizumab or sunitinib alone, and we saw the efficacy data in February, and here we're seeing the quality of life outcomes, and looking at how patients are doing, patient-reported outcomes on these treatments. And so with multiple quality of life measures, we're seeing improvements in patients that had better disease-related scores of symptoms when treated with lenvatinib and pembrolizumab versus sunitinib. We're seeing pain scores improve and patients having less diarrhea, appetite loss, when we're comparing against sunitinib. Of note, it's hard to specifically tie a particular symptom, if that's improved, because they've had better disease control or if it's more from the treatment side effect itself. So still hard to tease out a causality in these quality of life measures, but overall, improvement in patients' quality of life when treated with lenvatinib and pembrolizumab. And certainly provides some more data for patients receiving this combination. And so I just wanted to highlight our ongoing phase 3 combination trials and first-line metastatic kidney cancer. PIVOT-09 with bempegaldesleukin has completed accrual in the first triplet of COSMIC-313 with ipilimumab, nivolumab and cabozantinib has completed accrual, so the actively enrolling studies currently are PEDIGREE and PROBE. These are studies that are being carried out in the cancer cooperative groups, as well as a triplet belzutifan lenvatinib with pembrolizumab, a study that Merck is running and all 3 very important studies we will continue to learn from and answer some important, clinically relevant sequencing treatment discontinuation, nephrectomy side effect questions. Thanks to everybody. Greg Guthrie: We have 1 more. So, “Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.” Dr. Zhang: Dr. Rodriguez from Spain presented this of papillary renal cell carcinoma treated with savolitinib and durvalumab, and specifically looked at the MET-driven subset of 14 patients out of these 42 patients. The efficacy primary end point was objective response rate. And of note, and median progression-free survival for the 42 patients who were all treated, it was 4.9 months and in MET-driven disease, so savolitinib targets MET, so MET-driven disease was 10.5 months and the median overall survival in everyone was 14 months, versus MET-driven was 27 months, and also higher response rates for patients with MET-driven disease. So I think personally, hypothesis generating, we will likely be seeing more trials with durvalumab and savolitinib in MET-driven papillary renal cell carcinoma. Greg Guthrie: Thank you, again, Dr. Zhang. And Dr. Gilligan, we're going to talk about some testicular cancer research now, and the first study is, “Testicular cancer in the cisplatin era: causes of death and mortality rates in a population-based cohort.” Dr. Gilligan: So this study was looking at what happens with testicular cancer patients who are cured of their cancer, are they at risk of dying of other causes? They looked at over 5,000 men treated between 1980 and 2009, so it's important to recognize that some of the treatments given back then are a little different than the way they're given now. And it looked at the risk of death from causes other than testis cancer compared to men without testicular cancer in the general population, and the concerning finding from this study, and it's not the first study to report this, was that the risk of non-testicular cancer death, that is, death from other causes, was increased by about 28% in men who had been treated with radiation therapy and about 23% in men treated with chemotherapy. There's a risk of non-testicular cancer death, the risk, excuse me, was doubled in those whose treatment included both. So it was higher with either radiation or chemo and it was actually 100% higher or double than both those who had chemotherapy and radiation. As you got more chemotherapy, the risk went up. There was no trend towards the increase with just 1 or 2 cycles. We started to see the increase with 3 cycles, and it became statistically significant with 4 cycles. But there wasn't much difference between 3 and 4 in terms of the absolute number that was seen. In terms of death from other cancers, so why is this happening? Other cancers are a major issue after chemotherapy or radiation. Again, the risk was increased 60% after radiation therapy and 43% after chemotherapy, and those who got both, the risk of cancer was 3 times higher than the general population. So that's in men who had chemotherapy plus radiation therapy. Fortunately, there are not a lot of men who get both of those treatments anymore. Non-cancer deaths increased 17% after chemo and 55% of treatment included both. So the risk for non-cancer deaths was not as high as the risk for death from secondary malignancies. Interestingly, the risk of suicide increased 63% in men treated with chemotherapy. That's not affecting as many men as those other numbers, even though 63% number looks high, but it is a concern. Those treated only with surgery did not have an increased risk of non-testicular cancer death. What does this mean for patients? It really means when we can use surgical treatments instead of chemotherapy or radiation as an additional incentive to try do that, and what that may mean is there should be a larger role for retroperitoneal lymph node dissection as an alternative to chemotherapy or radiation therapy. Secondly, for patients getting chemotherapy, it's important to minimize the number of cycles of chemo as long as we're not sacrificing long-term cure rates, because the biggest risk of death is dying from the cancer, but that means limiting to the 3 cycles instead of 4 cycles is probably a good idea, and I think it's an argument to use 3 cycles of BPE instead of 4 cycles of EP because it's really the etoposide and the cisplatin that is linked to the secondary cancer risk, not the bleomycin, as far as we know. And then lastly, we need to pay attention to the mental health needs of men treated with chemotherapy. That there is more emotional distress and we're seeing here a higher risk of suicide. Greg Guthrie: So our second trial is the, “SEMS trial: result of a prospective multi-institutional phase 2 clinical trial of surgery in early metastatic seminoma.” Dr. Gilligan: So if we're going to use more retroperitoneal dissection and less chemotherapy or radiation, 1 place to do that is in stage 1 and stage 2 seminoma, and many centers around the country have started doing that, and this was a trial that looked at that approach. So these are men who normally would be treated with chemotherapy, 3 cycles of BEP, or radiation therapy to the back of the abdomen and part of the pelvis potentially. This study looked at the small number of patients, 55 men, low volume, stage 2 seminoma up to 3 centimeters of size and maximum dimension. And what they reported of those men undergoing retroperitoneal lymph node dissection, 10 relapsed, so 18% relapsed after median follow-up of 24 months, they were all alive at the end of the study. No deaths. 8 of 10 relapses were treated with chemotherapy, and 2 were treated with additional [surgery]. Out of the 55 men, 8 ended up getting chemotherapy. Normally, all of them would have gotten either chemo or radiation. Relapse-free survival was 87%, overall survival was 100%. Seven (7) patients developed complications after RPLND and 5 of them were mild. Two (2) were more severe. So it's a well-tolerated treatment, if it's done at a large volume center, it's worth noting that the centers participating in the study were large volume centers. Again, if not treated with RPLND, all of these men would have gotten chemo or radiation. The relapse rate after chemotherapy or radiation is about 5%. So the relapse risk is higher after surgery, but in the sense, if we take 100 men with early stage 2 seminoma and do an RPLND instead of chemo or radiation, we can spare 80% of them the long-term effects of chemotherapy or radiation. Alternatively, if the priority is simply to prevent a relapse, radiation therapy and chemotherapy are more effective at that, the relapse risk being 5% but at the cost of long-term side effects from chemotherapy or radiation. Bottom line there is an additional treatment option for low volume stage 2 seminoma for men who prioritize avoiding the complications of chemotherapy or radiation therapy. Both of which are associated with an increased risk of death from other causes. The price we pay for that is the relapse risk is higher with RPLND compared to the other approaches. Not all centers are going to be offering this, but major centers that do a lot of testicular cancer, this is becoming a new treatment option. With the caveat that we have less experience with this approach. This is a relatively small study. And we have a lot more experience with chemotherapy or radiation. I don't think there's a one size fits all here, but I think patients should talk about it with their doctor. If they have early-stage seminoma, they should talk about surgery as an alternative to radiation or chemo. Greg Guthrie: Here we go. “Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor.” Dr. Gilligan: So this study is looking at the question, if you take a man who has retroperitoneal lymph nodes that are enlarged and metastatic non-seminomatous testis cancer with lymphadenopathy in the back of the abdomen and you put them through chemotherapy and at the end, all retroperitoneal nodes are now within normal limits, normal size nodes, and no bigger than 10 millimeters or 1 centimeter, do we need to do a retroperitoneal lymph node dissection on those patients? Some centers recommend it and some don't. This looked at 388 men in that situation. They were put on surveillance. These men did not undergo the post-chemo RPLND. Two years survival, overall survival was 97.8%. Two-year progression-free survival was at 90%, 34 patients relapsed, and 10 of the men died. Men who did relapse had surgery, chemotherapy, or both as subsequent treatment. There's a prior similar study that was multicenter that had longer follow-up of 5 years, and they reported of ;161 men who had a complete response to the first-line chemo, 10 relapsed (that's 6%) and none died. If we combine these 2 studies together, the bottom line is you would have to perform a post-chemotherapy retroperitoneal dissection, which is a big operation, on about 550 men to prevent potentially at most 44 relapses and 10 deaths. We don't know if we would prevent or how many of those relapses and deaths we would prevent. But there's a lot of operations with a relatively low yield. In the future, we hope to have blood tests that will tell us which men need surgery. And even right now, we're close to the point that we have blood tests that will detect residual cancer. And the chance is we worry about residual cancer in these patients and we don't have the blood test to pick it up. But the bottom line is in the meantime, the preferred management strategy is surveillance rather than surgery for most men. There's some men for whom RPLND may make sense in the center in this setting and some centers that will probably continue to recommend it for most men. I think this data really casts doubt on whether we ought to be doing this operation in these men as a routine practice as opposed to an exceptional practice for men who have particular characteristics. Thank you. Greg Guthrie: Thank you, Dr. Gilligan. And now we can move on to answering some questions. What is the average time expected to see a decline in PSA in patients treated with lutetium-177 PSMA? Dr. Agarwal: I think this a great question and I think we're waiting for the manuscript published to go through the nuances of those data. Right now, what Dr. Michael Morris from Memorial Sloane-Kettering presented were the high-level data on pre-survival and overall survival and some secondary endpoints. We are anxiously waiting the full data in the form of a manuscript. And until then, I will not be able to answer that question. I would like to add that usually the median time, if you look at how -- for how long patients were receiving lutetium, it was 5 to 6 months. If I -- if my recollection is correct. Greg Guthrie: Is radiation required prior to initiating chemo if there's tumor presence? And Dr. Gilligan, you responded. “We rarely use radiation therapy for testicular cancer at this time. Sometimes it is used for stage 1 or stage 2 seminoma as primary treatment instead of chemotherapy.” And I'll just read these aloud for our viewers here. If a patient has both prostate and bladder cancer, how do you decide which therapy should take priority, also, is the CPS typically included on the biopsy report? And Dr. Grivas, you responded, which I'll read here. “This is a bit of a complicated scenario that requires detailed discussion with a urologist and medical oncologist. Regarding CPS, the possible role is only in the first-line setting of metastatic disease to help somewhat decide between chemotherapy followed by avelumab maintenance and immunotherapy. However, it's not a perfect biomarker and not part of the pathology report, it's a special test that requires specific ordering.” I have a question for you, Dr. Zhang. Why do combination treatments seem to work better in kidney cancer? Wouldn't you have more side effects because you're taking 2 drugs at the same time? Dr. Zhang: It's an interesting question. You know, our immunotherapy backbones seem to have good treatment benefit for these immune responsive diseases. The VEGF inhibitors that blocked blood vessel formation for many of our patients with clear cell kidney cancer, they tend to have an immunomodulatory role, so if we normalize blood vessels in the tumor microenvironment, the thought is that the T cells and immune cells can actually get into that space more readily. And so many of these blood vessel blockers are hypothesized to have increased immunomodulatory times of behaviors and the combination actually can be more effective than either agent alone, and we've certainly seen that in practice and really excited to see these combination strategies thrive and be standard of care for our patients now and first-line treatment. For the side effect question, you know, I do think that sometimes we do have to tease out which of the side effects is related to the oral treatment, the blood vessel blocker versus the immune therapy. But it's often experienced oncologists who are able to manage these side effects. We can try to tailor and see which of the side effects is due to which treatment and how to reduce or hold treatments when necessary. Greg Guthrie: Great. I just got a follow-up question for you, Dr. Zhang. Are there any studies for papillary type kidney cancer with sarcoma? Dr. Zhang: I would assume you're asking about sarcomatoid renal cell carcinoma within papillary, so for papillary type of kidney cancers, there are ongoing studies. For example, with FH mutations and FMH loss. For sarcomatoid disease, this is a special type of histology that can occur with any of our actual histologies of kidney cancer. And we know from our phase 3 trials in clear cell sarcomatoid renal cells that these tend to respond to the immunotherapy combinations. And so I would urge using an immune therapy combination in patients who had sarcomatoid renal cell carcinoma. Greg Guthrie: Dr. Agarwal, here is a question for you. There were several studies in here that showed many patients did not receive combination ADT with other novel therapies, which you describe as the standard of care, including the one you discussed. Is this something that patients should proactively bring up with their doctors? Dr. Agarwal: Fantastic question. I'm so glad you asked. The answer is yes: It is our responsibility as physicians and providers, but it doesn't hurt if our patients are educated and challenge us in our decision-making. It is a shared decision-making, it is not the doctor's decision. In my view, it's the patient's decision with help from the doctors. So, yes, please go do it. Doctors usually welcome that. Greg Guthrie: Great. Dr. Grivas: I see one for Dr. Gilligan about surveillance imaging that just popped up. [Is there any data on the benefits vs. risks for imaging based surveillance (CT, MRI, none) for longer-term follow-up periods (e.g. 2+ years)?] Dr. Gilligan: Yeah, they're asking whether there's data on benefit versus risk for imaging-based surveillance and it's actually a very timely question in the sense that we're starting to get data that MRI is very accurate for this. And may likely become a substitute for CT scans at some point in the future. This is something we talk about a lot in terms of surveillance for testicular cancer patients, can we switch to MRI from CT because CT has ionization that can cause other cancers, and MRI does not. The good news is it looks like with current CT scanning, which is lower dose than older CT scanning, the risk of cancer from the CT scan seems really miniscule. Ultimately, it would be great to get it down to 0 and not do them, but we're still doing them. The switch to MRI is being held up by the fact that when you go in and get an imaging study for surveillance, your scans get looked at by a radiologist and also by the oncologist and all of us who do a lot of testicular cancer have multiple stories of catching stuff that the radiologist missed, and they also catch stuff that we miss. It goes both directions, and we're having 2 different people read the films to get a more accurate read. With MRI, most oncologists are not competent to read an MRI well and some radiologists are not great, and the centers where they have excellence have shown that MRIs are just as good as CT scans if read by fully qualified people. And the concern is: are they going to be skillfully read? So the switch to MRI will happen in the future, and I have spoken with people very recently about this that are practicing around the country and the people I talked to were not ready to make the switch because of the concern that stuff might get missed. And I think we can be reassured with the modern lower-dose CT scans, the risk seems to be quite small, and I look forward in the future to making that switch at some point. Greg Guthrie: And I think that's going to be our last question this afternoon. Thank you to all our participants for sharing this great research with us, as well as your expertise, it's been a real pleasure on this live webinar here. ASCO: Thank you Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate. This presentation is provided solely for informational purposes. The ideas and opinions expressed in this presentation do not necessarily reflect the views of the American Society of Clinical Oncology (ASCO) or its affiliates. The mention of any product, service, or therapy in this presentation should not be construed as an endorsement of any product, service, or therapy mentioned. The information herein does not constitute medical or legal advice, and is not intended for use in the diagnosis or treatment of individual conditions or as a substitute for consultation with a licensed medical professional. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the presentation or any errors or omissions. © ASCO 2021, all rights reserved.
A RT, juntamente com a supressão androgênica (AS), é uma opção de tratamento padrão para pacientes com câncer de próstata localizado de alto risco. Com a hipótese de que a adição de QT com docetaxel poderia melhorar a sobrevida global dos pacientes este estudo foi criado. Recrutados entre 2005 e 2009, pacientes com doença não metastática de alto risco foram randomizados receber SA mais RT com ou sem docetaxel adjuvante......Ainda que “vintage”, esse esquema melhorou a SG de 89% para 93% em 4 anos, com melhora da sobrevida livre de doença e redução na taxa de metástases à distância. Foi, portanto, um estudo positivo, sugerindo que docetaxel pode ser uma opção de tratamento a ser discutida em pacientes de alto risco. .....Para ler o paper na íntegra, acesse: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506419/
O estudo CA184-043 avaliou a RT para metástases ósseas seguida por ipilimumab ou placebo em homens com câncer de próstata metastático resistente à castração (mCRPC) que haviam recebido docetaxel previamente. No entanto, em uma análise anterior, o desfecho primário (SG) foi negativo.Esse paper, relata os resultados finais daquele estudo, com um tempo adicional de acompanhamento de 2,4 anos, conseguindo recrutar cerca de 800 pacientes.Apesar do resultado positivo a favor do braço ipilimumab, esse estudo foi considerado “gerador de hipótese”.Saiba do porquê disso neste episódio! Sejam bem-vindos a mais um episódio do Clinical Papers Podcast! Acesse o paper através do link:https://www.europeanurology.com/article/S0302-2838(20)30604-7/fulltext
Comment bien lire un article original ?Exemple pratique avec les études CHARTEED et STAMPEDEQuid des conclusions à partir des analyses en sous-groupe ? Le Pr N. MOTTET (CHU de Saint-Etienne) répond à toutes vos questions ! L’orateur n’a pas reçu de rémunération pour la réalisation de cet épisode. Pour aller plus loin :CHARTEED Sweeney, et al. « Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer ». The New England Journal of Medicine 373, no 8 (20 août 2015): 737‑46.Lire ici STAMPEDE : James, et al. « Addition of Docetaxel, Zoledronic Acid, or Both to First-Line Long-Term Hormone Therapy in Prostate Cancer (STAMPEDE): Survival Results from an Adaptive, Multiarm, Multistage, Platform Randomised Controlled Trial ». Lancet (London, England) 387, no 10024 (19 mars 2016): 1163‑77.Lire iciSTAMPEDE radiothérapie : Parker, et al. « Radiotherapy to the Primary Tumour for Newly Diagnosed, Metastatic Prostate Cancer (STAMPEDE): A Randomised Controlled Phase 3 Trial ». Lancet (London, England) 392, no 10162 (01 2018): 2353‑66.Lire ici Réalisé avec le soutien institutionnel du laboratoire JanssenMusique du générique : Via AudioNetworkResponsable projet AFUF : Dr Benjamin PradèreProduction : La Toile Sur Ecoute See acast.com/privacy for privacy and opt-out information.
This week, we'll start with a report on end-of-trial findings with a triplet combination treatment for HER2-positive metastatic breast cancer. Then, we'll hear from the director of a comprehensive cancer center on how her institution is handling the coronavirus outbreak. Lastly, we'll discuss the FDA's approval of durvalumab in small cell lung cancer.Coverage of stories discussed this week on ascopost.com:End-of-Study Results From CLEOPATRA: Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast CancerFDA Approves Durvalumab as Part of a First-Line Combination Regimen for Extensive-Stage SCLC
For many people, chemotherapy conjures up thoughts of debilitating sickness and end of the line therapy. Today this is no longer the case. With advancements in modern medicine, side effects from chemotherapy can be easily managed and reduced. Chemotherapy treats metastatic disease and prevents relapse in men with prostate cancer. This episode of PROSTATE PROSContinue reading
This week, we'll be discussing findings presented at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer and the ASCO Quality Care Symposium, including a pooled analysis on 5-year overall survival rates in patients with previously treated non-small cell lung cancer receiving nivolumab vs docetaxel; the effect of out-of-pocket costs of tyrosine kinase inhibitors on survival in patients with lung cancer; and the relationship between participation in a clinical trial and overall survival in patients with advanced lung cancer.Coverage of stories discussed this week on ascopost.com:WCLC 2019: Pooled Analysis of CheckMate 017 and 057: 5-Year Outcomes With Nivolumab vs Docetaxel in Previously Treated NSCLC2019 Quality Care: Cost of Treatment, Prior Authorization of Treatment Plans May Cause Barriers to Care2019 Quality Care: Clinical Trial Enrollment May Be Associated With Reduced Mortality in Patients With Metastatic Lung Cancer
Welcome to the ASCO Daily News Podcast. I'm Dr. Richard Schilsky, senior vice president and chief medical officer of ASCO. I am pleased to be joined by Dr. Christopher Sweeney, a medical oncologist and professor of medicine at Harvard Medical School and Dana Farber Cancer Institute. He presented abstract LBA2 entitled overall survival results of a phase three randomized trial of standard of care therapy with or without enzalutamide for metastatic hormone sensitive prostate cancer, the ENZAMET trial, an ANZUP led international cooperative group trial. Dr. Sweeney, welcome to the podcast. Thank you for having me. So testosterone suppression and androgen receptor blockade, of course, have been the cornerstone of treatment for men with advanced prostate cancer for many, many years. This large trial of men with metastatic hormone sensitive prostate cancer demonstrated an overall survival advantage by substituting enzalutamide for older androgen receptor blockers. Tell us more about how the patients did on this treatment. Well, the first big line item to report is that men who got the drug enzalutamide, which, as you point out, is the more potent version of the way to block the androgen receptor than our old drugs, lived longer. In terms of relative risk, men had a 33% chance of being alive longer than men who got the older drugs. In terms of absolute numbers, 80% of men who got the early drug were alive at three years versus 72%. What's buried in all those numbers, though, is that there are different patient populations. Patients who have a higher burden disease, have a faster progression, and, unfortunately, a shorter survival than men who have a lower burden of disease. With our previous iteration of this type of a trial in men starting hormones, we showed that docetaxel benefited patients who had high volume disease very clearly. And we could also see enzalutamide works just as well with docetaxel in that patient group. On the other hand, men who had a low burden of disease, we didn't really see a benefit with chemotherapy docetaxel. But we did see a big benefit here in this study with using the hormone enzalutamide. So that now comes to the question, well, what about men who are treated with docetaxel? Did enzalutamide help them? And we actually had a group of patients in this study who we can pull out and analyze separately. And we can see that the enzalutamide delayed the time to progression when it was added to the docetaxel. But at this early analysis, we don't see any meaningful impact in survival. And that could well be because men who get the hormones and the docetaxel and then have the drugs, like enzalutamide, do just as well as getting all three drugs upfront, testosterone suppression, docetaxel, and the enzalutamide, do just as well as getting docetaxel, testosterone suppression, followed by enzalutamide. So it's a little bit of a parsing out of who the patients were and what treatments they get to work out how they actually fared. Tell us a little bit more about enzalutamide. This is a drug that's already FDA approved. It's already in use for later lines of therapy. How does it differ from the earlier group of androgen receptor blockers? Do you attribute all of the benefits seen in the enzalutamide group to the drug itself, or were there differences in patient populations perhaps from groups studied with the earlier generation of androgen receptor blockers? It seems like a pretty substantial improvement just by swapping out a newer version of an old drug. Yes, that's a very interesting observation. So the first notion is that the drug was tailored and designed by chemistry to be a much more potent version of the old drugs. So they're able to see the crystal structure of the androgen receptor and then do chemistry to say, how can we block that and shut that receptor down more efficiently? What is unique about the trial design, because we ran this as an academic study, is that we incorporated in a control arm, every patient had to have one of the older less potent drugs as a control to really show that the more potent drug did actually have all the benefits and conferred the benefits over the older drug. So it wasn't versus a non-active placebo. So it's very clear as a direct more potent versus less potent drug, we had a survival benefit. The other thing to note is that we had clues that this may work is because patients who have testosterone suppression and when their cancer progressed, they had an up regulation of the androgen receptor. So the cells say, help me, help me. I need more testosterone or testosterone like hormones to live. And it up regulates that receptor to survive. And it becomes a target that we can use. Whereas the older drugs would be able to bind to it. But sometimes, they actually became agonists. They turned the receptor on rather than turning it off. Where this drug has complete antagonistic turning the receptor off properties. So it's really quite a clear more potent drug versus less potent drug leading to the survival benefit across both patients with a poor risk, higher volume disease and a lower risk, lower volume disease. It's really interesting how understanding the structure of the androgen receptor and the chemistry of the drug really seems to have led to a very substantial improvement in patient outcomes. So this is a drug, as I mentioned earlier, that's already FDA approved, although in another line of therapy, but could potentially be substituted into routine clinical care immediately. Do you think the study results justify making that switch? It's a very important question. So another way to phrase what you just said there, Rich, is we're seeing advances in advanced stage disease. And my mantra is let's go forward by moving backwards into the earliest stage disease where the patients are starting the hormone not when they're progressing on the testosterone suppression. So when they're starting the hormones, we actually see a survival benefit when we give it upfront. That is a new indication. And so it will be up to the developer of the drug, which is both co-developed by a company called Pfizer and [INAUDIBLE], to present that to the FDA and see if it will get a label extension from the castration setting, resistance setting to the hormone sensitive setting. So that's a work in progress. Now the important item is to recognize that to be able to access the drug, there's going to have to think through the side effect profile. And there are some side effects with regard to it can cause a little bit more fatigue, a little bit more impairing concentration because of the way it works. And some patients can feel a little bit more frail. So some patients have these side effects, and there have to be dose modifications. So the risk and benefit profile has to be adjudicated. But by patients living longer and having their cancer controlled for longer, most patients do get a benefit. But the flip side is we also have to work out other alternatives. Docetaxel is an alternative for patients with high volume disease. Abiraterone is another drug that's approved in this setting, which is another different type of a hormone. And when we write for these drugs, we have to adjudicate how much the patient is going to have to pay. Some patients, they have a copay of $5. Other patients, a copay of about $2,500, because these drugs are very expensive. And if patients have no insurance, the cost is close to $9,000. So I think it is a very good option that will emerge. I suspect it will get approved. But when patients are counseled by their physicians on the options, they have to review the side effects, the benefits, as well as the financial access issues. Yeah, very important points to bring up. So it always comes down to risks, benefits, and costs, and how that translates into access. So just to wrap up, obviously, prostate cancer is a very common disease. As our population continues to age, I think we can foresee that it may become even more common in the population. What's on the horizon for prostate cancer research and treatment? This is a disease where there's been a considerable amount of progress has been made in recent years. But perhaps, there's going to be a growing medical need as the population continues to age. So where do you see the future in prostate cancer research? So the first thrust of work that I'm actively involved in and have engaged with collaborations around the globe to do more trials is to go even further back into the disease setting and augment the adjuvant therapy around the time of prostate radiation or prostate surgery to decrease the risk of relapse. So we have less patients who actually develop metastatic disease and die of the disease. So a lot of us are now getting very proactive in that setting. The other setting is profiling the tumors to work out which patients would be better treated with our current chemotherapy, be it the hormones, be it the combination, as well as develop new drugs that target new targets that are identified. So early identification and more aggressive proactive treatment to prevent relapses. And if patients do relapse, interrogate the tumors more to get more informative data on how best to treat the patient with which new drugs that emerge. So just along those lines actually, your comment prompted a thought. One of the other abstracts presented in the plenary session was about a PARP inhibitor for maintenance therapy in patients with pancreatic cancer, certainly a difficult disease to treat. There's been some preliminary evidence that PARP inhibitors may have activity in prostate cancer as well. Do you think that's going to be an emerging molecular target in prostate cancer? I definitely think it will be. And to some degree, it already is a player. What we need to do is being conducted are the proper rigorous trials to work out, which is the genomic profile that of the DNA damage repaired defects in the genes like the BRCA2 gene you're referring to, that actually do portend a potential response. So we see that the DNA damage genes, response genes that may portend a response to a PARP inhibitor are about 20%. But maybe half of those are truly the genes that really are the responders, that define the responders. And the question now is, of those particular genes that are refined, how many of those actually respond and how long? So we're seeing, I would say, responses of about 50% in that subgroup. So it is very much the notion of precision medicine, because it's the precise group of patients, which inherently is a small subset, but a subset that we can identify and potentially give a meaningful treatment with a reasonable side effect profile. So that data should emerge over the next 12 to 24 months, I think, based on the status of the trials. Great. Thanks so much for giving us that little glimpse into the future. So again, today, my guest has been Dr. Christopher Sweeney from Harvard Medical School and Dana Farber Cancer Institute. Chris, thanks so much for being on the podcast today. It was my honor. And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts
Welcome to Prostate Cancer & You, a series of podcasts sponsored by the Massachusetts Prostate Cancer Coalition. Today’s podcast features an interview with Glenn Bubley, MD, director of the Division of Genitourinary Medical Oncology at the Beth Israel Medical Center and associate professor of medicine at Harvard Medical School. He is the 2009 recipient of the Jack Colbert Memorial Award. On this podcast he discusses the good news about new treatments for metastatic and non-metastatic prostate cancer. Important clinical trials have been performed that have shown that earlier treatment of metastatic disease with combinations of existing agents have provided a major improvement in overall and cancer specific survival. This includes combinations of hormonal agents like Lupron with Abiraterone or Lupron with the chemotherapeutic agent Docetaxel. At the May 10 Prostate Cancer Symposium his session is “Newer Therapeutic Strategies for Advanced Prostate Cancer.” Go here for more information and to register.
Dr. Daniel Goldstein summarizes findings of a trial presented at ASCO 2018 by Dr. Kellolumpu-Lehtinen, assessing the benefit of adjuvant docetaxel for patients after radiation for patients with high or intermediate risk localized prostate cancer.
This commentary examines whether patient-reported outcomes were substantially different in men given chemohormonal therapy versus hormone therapy in the CHAARTED randomized controlled trial. Related Article: Quality of Life During Treatment With Chemohormonal Therapy: Analysis of E3805 Chemohormonal Androgen Ablation Randomized Trial in Prostate Cancer
Dr Gwenaëlle Gravis talks to ecancertv at ASCO GU 2015 about the results of the GETUG-AFU 15 phase III trial. Long-term follow-up results suggest that the addition of docetaxel to androgen deprivation therapy did not significantly improve overall survival in patients with hormone-naïve metastatic prostate cancer.
Dr Barlesi presents, at a press conference at ESMO 2016, results from the OAK study, which found atezolizumab improved median overall survival for patients with advanced non-small cell lung cancer, especially those stratified by high PD-1 expression.
Dr Eljertsen speaks with ecancertv at SABCS 2016 about a trial regimen for the treatment of early breast cancer, of 3 cycles of epirubicin and cyclophosphamide (EC) before 3 cycles of docetaxel and cyclophosphamide (CD), compared to 6 cycles of the latter. He describes the addition of anthracyclin treatment as having no clinical benefit for patients with a non-mutated TOP2 gene, resulting only in increased toxicity. Given that Dr Eljertsen estimates only 15% of tumours express a TOP2a mutation, added anthracyclin treatment ought to be deferred in the majority of patients.
Dr Alibhai speaks with ecancertv at SIOG 2016 about the experience of men receiving abiraterone or docetaxel for the treatment of metastatic castrate resistant prostate cancer. He discusses how the efficacy was similar to prior published studies, and how toxicities were slightly greater.
Dr Ahlgen speaks with ecancertv at ASCO 2016 about the results of SPCG12, a randomised phase III trial assessing patient survival following radical prostatectomy with docetaxel. Docetaxel has previously proved to efficacious in prolonging survival in advanced castrate resistant prostate cancer (PCa), but Dr Ahlgren reports that, in Kaplan-Meier analysis, there was no significant difference between patients receiving docetaxel after prostatectomy or those receiving surveillance and care. He highlights that docetaxel as a monotherapy seems to generate a more rapid biochemical progression in a subgroup of patients, and that further analysis of this subgroup is warranted.
Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.
Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.
Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.
Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.
Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.
Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.
Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.
Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.
Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.
Dr. Heather Wakelee, Stanford University Medical Center, lists standard adjuvant chemotherapy regimens, comparing their administration and uses.
Dr. Heather Wakelee, Stanford University Medical Center, lists standard adjuvant chemotherapy regimens, comparing their administration and uses.
Dr. Heather Wakelee, Stanford University Medical Center, lists standard adjuvant chemotherapy regimens, comparing their administration and uses.