Podcasts about Ipilimumab

Making strides against melanoma: how can medical oncologists and interventional oncologists join forces to deliver smarter, patient-centered care? In this episode of BackTable, Dr. Tyler Sandow, hosts Dr. Sunandana Chandra, medical oncologist at Northwestern, and Dr. Riad Salem, interventional oncologist at Northwestern to discuss the evolving management of advanced melanoma. --- This podcast is supported by an educational grant from Replimune. --- SYNPOSIS The doctors open the episode with an overview of melanoma and recent advances in its treatment, highlighting key trials such as DREAMseq and CheckMate 067. The discussion explores the shift from medical oncologist as solo primary providers to a dynamic, multidisciplinary approach to advanced cancer care—emphasizing cutting-edge treatments like immunotherapy and intratumoral oncolytic viruses. Dr. Salem shares practical insights on the procedural techniques of administering intratumoral oncolytics like Replimune, emphasizing the importance of thorough documentation and patient-centered care. The doctors also provide an overview of the ongoing IGNYTE-3 Trial, a Phase 3 study assessing the safety and efficacy of the oncolytic immunotherapy RP1 in combination with nivolumab for the treatment of advanced melanoma. The episode underscores the transformative potential of innovative melanoma treatments and the crucial role of integrated, team-based approaches in improving cancer patient outcomes. --- TIMESTAMPS 00:00 - Introduction03:48 - The Evolution of Melanoma Treatment: From Chemotherapy to Immunotherapy14:05 - The Role of Oncolytic Viruses in Melanoma Treatment20:14 - Interventional Radiology's Role in Cancer Treatment27:00 - Collaborative Approach to Cancer Care32:53 - Hyper Documentation and Communication Efficiency44:47 - Future of Intratumoral Oncolytics48:10 - Multidisciplinary Approach in Advanced Cancer Management51:46 - Conclusion and Final Thoughts --- RESOURCES DREAMseq Trial: Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. doi:10.1200/JCO.22.01763 CheckMate 067 trial: Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22. doi:10.1056/NEJMoa2407417

Según estudio: Combinar 2 fármacos ayuda a prolongar la vida de los pacientes con melanoma metastásico.Para hablar de ello nos acompañó el Dr. Jerónimo Rodríguez Cid, Oncólogo, Jefe de Oncología del Instituto Nacional de Enfermedades de Ciudad de México.La combinación de dos fármacos de inmunoterapia puede ser un tratamiento para los enfermos con melanoma metastásico avanzado, un cáncer agresivo y mortal, cuando es resistente a la terapia estándar actual, según un estudio que publicó, Nature Medicine.En los ensayos clínicos, los investigadores descubrieron que la terapia combinada puede extender la cantidad de tiempo que los pacientes viven sin que el cáncer empeore (supervivencia libre de progresión) y ayuda a superar la resistencia a las inmunoterapias anteriores, lo que permite que más personas se beneficien del tratamiento.El enfoque combinado de ambos fármacos “debería ser el régimen farmacológico preferido para las personas con cáncer que no han respondido a un tratamiento previo de inmunoterapia”, se comentó en un comunicado de la UCLA.El estudio, en el que participaron 91 personas, combinó los medicamentos de inmunoterapia Ipilimumab y Nivolumab.

Interview with Michael A. Postow, MD, author of Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy. Hosted by Vivek Subbiah, MD. Related Content: Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy

Interview with Michael A. Postow, MD, author of Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy. Hosted by Vivek Subbiah, MD. Related Content: Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy

In this episode, Alexa Basilio, PharmD, BCOP and Jessica Davis, PharmD, BCOP, CPP discuss immune-related adverse events and toxicities among patients using immune checkpoint inhibitors. This overview will include discussion about: How and when to monitor and treat mild vs severe immune-related toxicitiesThe art of balancing and tapering low-dose and high-dose corticosteroidsDifferentiating between immune-related and chemotherapy- or targeted therapy–associated adverse events for optimal management approachesInvolvement of multidisciplinary teams early during treatment to prevent immune-related adverse eventsImportance of educating patients, caregivers, and providers on immune-related toxicitiesPresenters: Alexa Basilio, PharmD, BCOPUniversity of Florida College of Pharmacy Oncology Pharmacy Specialist McKesson, The US Oncology NetworkTampa, Florida Jessica Davis, PharmD, BCOP, CPP Levine Cancer InstituteClinical Pharmacist Coordinator, Adult Hematology/OncologyAtrium Health Levine CenterCharlotte, North Carolina Link to full program: https://bit.ly/3We4HJy

In this JCO Article Insights episode, Rohit Singh provides a summary on "First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data", by Long et al, published in the November issue of the Journal of Clinical Oncology. The article provides insights into the use of the two dual immune checkpoint inhibitor regimens in patients with untreated advanced melanoma. TRANSCRIPT Rohit Singh: Hello and welcome to JCO Article Insights. I'm your host Rohit Singh, Assistant Professor at the University of Vermont Cancer Center and today we'll be discussing the article “First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trials,” authored by Dr. Georgina Long from the Melanoma Institute of Australia and her colleagues.  So as we know, nivolumab plus relatlimab and nivo plus ipi, I'm going to refer to as ipi-nivo moving forward, are dual immune checkpoint inhibitors regimens that are approved for treating patients with advanced melanoma based on the phase 2 and 3 RELATIVITY-047 and phase 3 CheckMate 067 trials respectively. Nivo plus relatlimab is the only dual PD-1 and LAG-3 inhibitor regimen approved for treating patients with advanced melanoma and relatlimab is the first in class human IgG4 LAG-3 blocking antibody. Ipi plus nivo is a dual PD-1 and CTLA-4 inhibitor regimen.  So this paper basically is an indirect treatment comparison using a patient level database from these trials and this pretty much was conducted because of the absence of head to head trials looking at different regimens in advanced melanoma in first line setting. In this trial, the authors tried to compare these two trials. However, it's always hard to compare two different trials and we usually don't do cross trial comparisons. The problem is that the groups might be different to begin with. For example, one group might have younger patients, healthier patients, while the other might have older or sicker. These differences can make it hard to tell if the treatment caused improvement or if the groups were different to begin with. In this trial, researchers use inverse probability of treatment weighting to adjust the baseline differences between the two patient groups or between these two trials. Inverse probability of treatment weighting is a method used in research to help make a fair comparison between two groups when studying how a treatment intervention works. Basically, IPTW helps level the playing field between the two groups or like two trials for this paper. So, it calculates the likelihood of receiving a treatment. For each person, for each patient, researchers estimate the chance they would have gotten the treatment based on their characteristics like age, health, condition, their baseline staging, and based on that they create weights. People who are less likely to get the treatment but did are given more weight, and those who are very likely to get the treatment are given less weight. The same is done for the group that didn't get the treatment, and then they rebalance the groups. By applying these weights the group becomes more similar in their characteristics as if everyone had an equal chance of getting the treatment. This way, IPTW helps researchers focus on the effect of treatment itself and other differences between the groups. It's like adjusting the scales to make sure you are comparing apples to apples.  The key outcomes the authors are looking at in this one was progression free survivals, overall survival, confirmed objective response rate, melanoma specific survival, and treatment related adverse events. Looking at the results of this cross comparison trial, first looking at the PFS or progression free survival, both regimens ipi plus nivo and nivo plus relatlimab, showed similar PFS. At 36 months, PFS was 36% in nivo-relatlimab versus 39% in the ipi-nivo regimen with a hazard ratio of 1.08 indicating no significant differences. Looking at the overall survival at 36 months, overall survival was 57% in both the treatment regimens with a hazard ratio of 0.14, again, indicating no significant differences. Now looking at another confirmed objective response rate, confirmed objective rates were similar between both treatment regimens after weighting, 48% versus 50% with an odds ratio of 0.91 suggesting comparable response rates between the two regimens. Looking at melanoma specific survival at 36 months it was 65% versus 62%. Both treatments had similar melanoma specific survival with a hazard ratio 0.86.  An interesting thing in these results was subgroup analysis. Subgroups showed larger numerical differences in efficacy which favored ipi-nivo over nivo-relatlimab that included acral melanoma with a hazard ratio of 1.42 and OS with a hazard ratio of 1.72 in favor of ipi-nivo. Similarly for BRAF mutant melanoma, it showed a confirmed objective response rate with odds ratio 1.54 and same applied to mucosal melanoma with odds ratio of 1.59 and patients who have high LDH more than two times upper level limit. Looking at the safety and adverse side effects, nivolumab plus relatlimab had fewer grade 3 or 4 treatment related adverse effect which is 23% versus 61% and fewer any grade treatment related adverse events leading to discontinuation which was 17% versus 41%, which means 41% of the patients in the ipi-nivo arm lead to discontinuation. However, I would like to add to that that ipi-nivo was conducted much earlier and at that time we were still kind of assessing and trying to understand the immunity adverse effects, how to manage them, which probably could have made discontinuation more common compared to a nivo-relatlimab trial. By that time we definitely had much more experience dealing with immunity adverse effects.A couple of things mentionable in this, notable rates of hepatic and GI grade 3 or 4 treatment adverse events were lower in nivo plus relatlimab than with ipi-nivo, although the onset of any grade endocrine GI hepatic or skin related treatment related adverse events occurred most frequently in both treatment arms and in less than three months from randomization.  So looking at all this data and looking at all this, it definitely seems like both the trials are very comparable in terms of efficacy, though nivo plus relatlimab seems to have a better safety profile. This trial does have some strengths. It does use the patient level data from two large well conducted trials allowing for a robust comparison and inverse weighting which would definitely better help balance baseline characteristics, enhancing the reliability of the results, and it does lead to comprehensive assessment of both efficacy and safety outcomes, and provides a holistic view of the treatments. Given all this, definitely the fact that it's a cross comparison trial which leads to a big limitation, as I already mentioned, like definitely two trials, it's hard to compare two trials which can have its own inherited biases. So it has some differences in trial design, conduct and follow up times. Small size subgroup analysis definitely limits the ability to draw definite conclusions from those groups. There's definitely some inherent uncertainty with direct head to head cross comparison trials.  Looking at the future direction I would take from this trial, if we can have a direct head to head trial because both of the treatments are proven first line setting, it will be comparing these two regimen that can definitely provide more definite evidence and further research is needed to explore the efficacy of these regimens in specific subgroups. As I mentioned in this, some subgroups showed increased benefit in the ipi-nivo regimen, however, they were very small sample size so we need more research exploring those subgroups. One other part in both these trials, patients with active brain mets were excluded. However, there's a phase 2 trial looking at ipi-nivo in active brain mets patients. So I think assessing patients with active brain mets moving forward is also a crucial part looking at, because often, patients with advanced melanoma develop brain mets. It does lead to some unanswered questions like long term survival and quality of life. How do these regimens compare in terms of long term survival and quality of life? While the study provides data on PFS and OS, long term survival and quality of life metrics are essential for understanding the full impact of these treatments. Optimal sequencing strategies: what are the optimal sequence strategies for these patients who progress on one regimen? There is data suggesting that patients may respond to alternative regimens after progression, but more research is needed to establish the best treatment sequence. And real world performance: how do these treatments perform in real world settings outside of clinical trials? Real world data can provide insight into the effectiveness and safety of these regimens in a broader patient population.  So, in summary, nivo plus relatlimab offers similar efficacy to nivolumab plus ipilimumab but a significantly improved safety profile, making it the potentially preferable option for patients with untreated advanced melanoma. However, results should be interpreted with caution due to limitations of cross trial analysis for certain subgroups like acral melanoma, mucosal melanoma, BRAF mutant melanoma, and patients with high LDH more than two times off upper normal limit. The trial showed that there's a trend definitely with ipi-nivo may be more beneficial. Also, today data on the use of nivolumab plus relatlimab in active brain mets has not been reported. Based on these existing data, ipi-nivo remains a standard immunotherapy for patients with active brain mets. Further research, including direct head to head trials is needed to confirm these findings and explore optimal treatment strategies.  Thank you for tuning into today's episode. We hope this detailed summary of the study comparing Nivolumab Plus Relatlimab and Nivolumab Plus Ipilimumab in advanced melanoma has been informative. This is Rohit Singh. Thank you again for listening to JCO Article Insights. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  

Did you miss the ESMO Congress 2024? Listen here: NEJM Editor-in-Chief Eric Rubin and NEJM Evidence Associate Editor Oladapo Yeku discuss research that was presented at the 2024 European Society of Medical Oncology annual meeting. Visit NEJM.org to read the latest research.

Beyond the Digest are bonus episodes to the DermSurgery Digest that include reviews of interesting and relevant articles in dermatologic surgery literature.  This episode features articles from the Journal of the American Academy of Dermatology and The New England Journal of Medicine.  Articles include:Excision margins for melanoma in situ on the head and neck- A single-center 10-year retrospective review of treatment with Mohs micrographic surgery; JAADAcne scarring- pathophysiology,diagnosis, prevention and education: Part I; JAADProcedural and surgical treatment modalities for acne scarring: Part II; JAADAssociation between dermatology follow-up and melanoma survival: A population-based cohort study; JAADCumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study; JAADNeoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma; NEJM“Beyond the Digest” contributors include Dermatologic Surgery Digital Content Editor Naomi Lawrence, MD; “Beyond the Digest” co-host Yesul Kim, MD; Ami Greene, MD; Tara Jennings, MD; Sydney Proffer, MD; and Katie Shawan, MD.Your feedback is encouraged. Please contact communicationstaff@asds.net.

This week on The Beat, Editor in Chief Joel Dunning focuses on all the latest news and clinical content in cardiothoracic surgery. In addition, Joel discusses outcomes after hybrid chemotherapy and surgery lung cancer treatment, mechanical circulatory support during revascularization, and research opportunities for early career investigators in cardiac surgery. He also talks about videos demonstrating tetralogy of Fallot repair, repair of post-intubation tracheal stenosis, and a recorded webinar on the Ross procedure. Before saying goodbye, he discusses upcoming events in CT surgery. JANS Items Mentioned Surgical Outcomes After Chemotherapy Plus Nivolumab and Chemotherapy Plus Nivolumab and Ipilimumab in Patients With Non-Small Cell Lung Cancer  Mechanical Circulatory Support During Surgical Revascularization for Ischemic Cardiomyopathy  Research Concepts and Opportunities for Early Career Investigators in Cardiac Surgery  CTSNet Content Mentioned Tetralogy of Fallot With Absent Pulmonary Valve: Repair by Anterior Translocation of Branch Pulmonary Arteries and Reduction Plasty  Post-Intubation Tracheal Stenosis: Tracheal Resection With Dorsal Mucosectomy and Primary Anastomosis  The Ross Procedure: Clinical Evidence, Surgical Technique, and Q&A  Other Items Mentioned CTSNet Events Calendar Disclaimer The information and views presented on CTSNet.org represent the views of the authors and contributors of the material and not of CTSNet. Please review our full disclaimer page here.

Drs. Neeraj Agarwal and Jeanny Aragon-Ching discuss several key abstracts to be presented at the 2024 ASCO GU Cancers Symposium, including sequencing versus upfront combination therapies for mCRPC in the BRCAAway study, updates on the CheckMate-9ER and CheckMate-214 trials in ccRCC, and a compelling real-world retrospective study in mUC of patients with FGFR2 and FGFR3 mutations. TRANSCRIPT Dr. Neeraj Agarwal: Hello, everyone, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of ASCO Daily News. I am delighted to welcome Dr. Jeanny Aragon-Ching, a genitourinary oncologist and the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters and oral abstracts that will be featured at the 2024 ASCO Genitourinary Cancer Symposium, which is celebrating 20 years of evolution in GU oncology this year.  You will find our full disclosures in the transcript of this podcast, and disclosures of all guests on the podcast at asco.org/DNpod.  Jeanny, it's great to have you on the podcast today to highlight some key abstracts for our listeners ahead of the GU meeting. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. It's an honor to be here. Dr. Neeraj Agarwal: Jeanny, as you know, this year we are celebrating the 20th anniversary of the ASCO GU Cancers Symposium, and judging from this year's abstracts, it's clear that this meeting continues to play a major role in advancing GU cancer research. Dr. Jeanny Aragon-Ching: Indeed, Neeraj. This year's abstracts reflect the important strides we have made in GU cancers. So, let's start with the prostate cancer abstracts. What is your takeaway from Abstract 19 on BRCAAway, which will be presented by Dr. Maha Hussein, and of which you are a co-author? As our listeners know, several PARP inhibitor combinations with second-generation androgen receptor pathway inhibitors, or ARPIs, have recently been approved as first-line treatment for patients with metastatic castrate-resistant prostate cancer, or metastatic CRPC, and the question of sequencing PARP inhibitors and ARPIs instead of combining them has emerged. From that perspective, the results of the BRCAAway trial are very important. Can you tell us a little bit more about this abstract, Neeraj?  Dr. Neeraj Agarwal: I totally agree with you, Jeanny. The BRCAAway study attempts to answer the crucial questions regarding sequencing versus upfront combination of therapies in the mCRPC setting. It is a phase 2 trial of abiraterone versus olaparib versus abiraterone with olaparib in patients with mCRPC harboring homologous recombination repair mutations. Enrolled patients had mCRPC disease and no prior exposure to PARP inhibitors or ARPIs or chemotherapy in the mCRPC setting and had BRCA1 or BRCA2 or ATM mutations. As previously mentioned, these patients were randomized to 3 arms: abiraterone monotherapy at 1000 milligrams once daily, or olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoint was progression-free survival per RECIST 1.1 or Prostate Cancer Working Group 3-based criteria or clinical assessment or death, so, whichever occurred first was deemed to be progression.   Secondary endpoints included measurable disease response rates, PSA response rate, and toxicity. This was a relatively small trial with 21 patients in the combination arm, 19 patients in the abiraterone monotherapy arm, and 21 patients in the olaparib monotherapy arm. It should be noted that 26% of patients had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% of patients had any prior exposure to an ARPI, and these were darolutamide or enzalutamide or in the non-metastatic CRPC setting.  The results are very interesting. The median progression-free survival was 39 months in the combination arm, while it was 8.4 months in the abiraterone arm and 14 months in the olaparib arm. An important finding that I would like to highlight is that crossover was also allowed in the monotherapy arms. Of the 19 patients receiving abiraterone, 8 crossed over to receive olaparib, and of the 21 patients receiving olaparib, 8 crossed over to the abiraterone arm. The median PFS from randomization was 16 months in both groups of patients who received abiraterone followed by olaparib or those who received olaparib followed by abiraterone. This is striking when compared to 39 months in patients who started therapy with the combination therapy of abiraterone with olaparib. Dr. Jeanny Aragon-Ching: Thank you so much for that wonderful summary, Neeraj. So the key message from this abstract is that combining olaparib and abiraterone upfront seems to be associated with improvement in PFS compared to just sequencing those agents. Dr. Neeraj Agarwal: Exactly, Jeanny. I would like to add that these results are even more important given that in real-world practice, only half of the patients with mCRPC receive a second-line treatment. Based on these results, upfront intensification with a combination of an ARPI plus a PARP inhibitor in the first-line mCRPC setting seems to have superior efficacy compared to sequencing of these agents. Dr. Jeanny Aragon-Ching: Thank you so much. Now, moving on to a different setting in prostate cancer, there were a couple of abstracts assessing transperineal biopsy compared to the conventional transrectal biopsy for the detection of prostate cancer. So let's start with Abstract 261. Neeraj, can you tell us a little bit more about this abstract? Dr. Neeraj Agarwal: Sure, Jeanny. So, in Abstract 261 titled "Randomized Trial of Transperineal versus Transrectal Prostate Biopsy to Prevent Infection Complications," Dr. Jim Hugh and colleagues led a multicenter randomized trial comparing these 2 approaches, so, transperineal biopsy without antibiotic prophylaxis with transrectal biopsy with targeted prophylaxis in patients with suspected prostate cancer. The primary outcome was post-biopsy infection. Among the 567 participants included in the intention-to-treat analysis, no infection was reported with the transperineal approach, while 4 were detected with the transrectal approach, with a p-value of 0.059. The rates of other complications, such as urinary retention and significant bleeding, were very low and similar in both groups. The investigators also found that detection of clinically significant cancer was similar between the 2 techniques and concluded that the transperineal approach is more likely to reduce the risk of infection without antibiotic prophylaxis. Dr. Jeanny Aragon-Ching: So the key takeaway from this abstract sounds like office-based transperineal biopsy is well-tolerated and does not compromise cancer detection, along with better antibiotic stewardship and health care cost benefits.  Moving on to Abstract 273, also comparing these two approaches, what would be your key takeaway message, Neeraj?  Dr. Neeraj Agarwal: In this Abstract 273, titled "Difference in High-Risk Prostate Cancer Detection between Transrectal and Transperineal Approaches," Dr. Semko and colleagues found that the transperineal biopsy based on MRI fusion techniques was also characterized by a higher possibility of detecting high-risk prostate cancer and other risk factors as well, such as perineural and lymphovascular invasion or the presence of cribriform pattern, compared to the conventional transrectal method. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So we can see that the transperineal approach is gaining more importance and could be associated with more benefits compared to the conventional methods.   Let's now switch gears to kidney cancer, Neeraj. Dr. Neeraj Agarwal: Sure, Jeanny. Let's start by highlighting Abstract 361, which discusses patient-reported outcomes of the LITESPARK-005 study. So what can you tell us about this abstract, Jeanny?  Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So as a reminder to our listeners, based on the LITESPARK-005 trial, it was a Phase 3 trial looking at belzutifan, which is an inhibitor of hypoxia inducible factor 2 alpha or I'll just call HIF-2 alpha for short, was very recently approved by the FDA as a second-line treatment option for patients with advanced or metastatic clear cell renal cell carcinoma after prior progression on immune checkpoint and antiangiogenic therapies. The title of Abstract 361 is "Belzutifan versus Everolimus in Patients with Previously Treated Advanced RCC: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study," and this will be presented by Dr. Tom Pells at the meeting. At a median follow-up of 25.7 months, the median duration of treatment with belzutifan was 7.6 months, while it was only 3.9 months with everolimus. At the time of data cutoff date for the second interim analysis, 22.6% of patients remained on belzutifan while only 5% remained on everolimus. In the quality of life questionnaires, the time of deterioration to various quality of life scores, as assessed by standardized scales, was significantly longer in patients randomized to the belzutifan arm compared to those in the everolimus arm. Also, patients in the everolimus arm had worse physical functioning scores. Dr. Neeraj Agarwal: Yes, Jeanny. In addition to the improved outcomes associated with belzutifan, patient-reported outcomes indicate better disease-specific symptoms and better quality of life among patients treated with belzutifan compared to everolimus. This is great news for patients with advanced renal cell carcinoma.  Now, Jeanny, can you please tell us about the two abstracts that reported longer follow-up of CheckMate 9ER and CheckMate 214 trials in untreated patients with advanced or metastatic renal cell carcinoma? Dr. Jeanny Aragon-Ching: Yes, Neeraj. So you are referring to Abstracts 362 and 363. Let's start with Abstract 362. This abstract reports the results after a median follow-up of 55 months in the CheckMate 9ER trial, comparing the combination of nivolumab and cabozantinib to sunitinib in patients with advanced RCC without any prior treatment, so first-line therapy. The primary endpoint was PFS per RECIST 1.1 as assessed by an independent central review. So there were key secondary outcomes including overall survival (OS), objective response rates, and safety. Consistent with prior analysis at a median follow-up time of 18.1 and 44 months, the combination of nivolumab and cabozantinib at a median follow up of 55.6 months continues to show a significant reduction in the risk of progression or death by 42% and in the risk of death by 23% compared to sunitinib.  Dr. Neeraj Agarwal: And Jeanny, what can you tell us about the efficacy results of this combination by IMDC risk categories? Dr. Jeanny Aragon-Ching: Similar to prior results in patients with intermediate to poor risk IMDC risk category, the combination treatment maintained significant efficacy and reduced the risk of progression or death by 44% and the risk of death by 27%. To put it simply, the update now shows a 15-month improvement in overall survival with the cabozantinib-nivolumab combination compared to sunitinib, which is amazing. Also, in patients with favorable IMDC risk group, which represented truly a small number of patients in the trial, there was a strong trend for improvement of outcomes as well. I would like to point out that no new safety concerns were identified. Dr. Neeraj Agarwal: So, it looks like the key message from this abstract is that with longer follow-up, the combination of nivolumab and cabozantinib maintains a meaningful long-term efficacy benefit over sunitinib, supporting its use for newly diagnosed patients with advanced or metastatic renal cell carcinoma.   Let's move on to Abstract 363, which compares nivolumab with ipilimumab to sunitinib in first-line advanced renal cell carcinoma. What would you like to tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Yes, Neeraj. The title of this abstract is "Nivolumab plus Ipilimumab versus Sunitinib for the First-Line Treatment of Advanced RCC: Long-Term Follow-Up Data from the Phase 3 CheckMate 214 Trial." In this abstract, Dr. Tannir and colleagues report outcomes with the longest median follow-up in first-line advanced RCC setting for any clinical trial. So the median follow-up now is about 18 months. The primary endpoints were OS, PFS, and objective response rates, as assessed by an independent review according to RECIST 1.1 criteria in the intermediate to poor risk IMDC risk group, which is the intent-to-treat (ITT) analysis, while secondary outcomes included the same outcomes in the ITT population of patients. Although the progression-free survival was similar in both arms, the combination of nivolumab-ipilimumab reduced the risk of death by 28% compared to sunitinib in the ITT population of patients. When stratifying the results by IMDC risk groups, the combination arm of nivolumab-ipilimumab showed significant improvement in the intermediate to poor risk group, but there was no difference in the favorable risk group. But in the study, no new safety signals were identified. Dr. Neeraj Agarwal: Thank you, Jeanny, for such a comprehensive description of the results of these two studies. I'd like to add that the median overall survival of patients with metastatic renal cell carcinoma in the ITT population in the CheckMate 214 trial has now reached 53 months, which would have been unimaginable just a decade ago. This is wonderful news for our patients. So the key takeaway from these two abstracts would be that immune checkpoint inhibitor-based combinations remain the backbone of first-line advanced renal cell carcinoma treatment.  Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. This is wonderful news for all of our patients, especially for those who are being treated for first-line therapy.  Now, let's move on to the bladder cancer abstracts. We have two exciting abstracts from the UNITE database. What are your insights on Abstract 537, titled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Switch-Maintenance of Avelumab in the UNITE Study"? Dr. Neeraj Agarwal: As our listeners know, enfortumab vedotin is an antibody-drug conjugate that binds to a protein called Nectin 4 expressed on bladder cancer cells. In this abstract, Dr. Amanda Nizam and colleagues describe outcomes in 49 patients receiving third-line enfortumab vedotin after prior progression on platinum-based therapy and maintenance avelumab. At a median follow-up of 8.5 months, the median progression-free survival was 7 months and the median overall survival was 13.3 months with enfortumab vedotin in this treatment-refractory setting, the objective response rates were 54%. The message of this study is that enfortumab vedotin is an effective salvage therapy regimen for those patients who have already progressed on earlier lines of therapies, including platinum-based and immunotherapy regimens. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for that comprehensive review.  I want to focus on another patient population in the UNITE database, which is the use of fibroblast growth factor receptor (FGFR) alterations. Can you tell us more about the sequencing now of erdafitinib and enfortumab vedotin in these patients with metastatic urothelial cancer, as discussed in Abstract 616? Dr. Neeraj Agarwal: Sure, Jeanny. As a reminder, erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma harboring FGFR2 or FGFR3 alterations after progression on platinum-based chemotherapy. However, the optimal sequencing of therapies in these patients is unclear, especially with enfortumab vedotin being approved in the salvage therapy setting and now in the frontline therapy setting.  So in this retrospective study, all patients with metastatic urothelial carcinoma had FGFR2 or FGFR3 alterations. Dr. Cindy Jiang and colleagues report outcomes in 24 patients receiving enfortumab vedotin after erdafitinib, 15 patients receiving erdafitinib after enfortumab vedotin, and 55 patients receiving enfortumab vedotin only. This is a multicenter national study. Interestingly, patients receiving both agents had a longer overall survival in a multivariate analysis, regardless of the treatment sequencing, than patients receiving enfortumab vedotin alone or only with a hazard ratio of 0.52. The objective response rate of enfortumab vedotin in the enfortumab vedotin monotherapy arm was 49%. When these agents were sequenced, the objective response with enfortumab vedotin was 32% after erdafitinib and 67% when used before erdafitinib. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. I think these are important real-world data results, but I would like to point out that larger and prospective studies are still needed to confirm these findings, especially regarding the outcome of erdafitinib after enfortumab vedotin, particularly when the latter is used in the first-line setting. Dr. Neeraj Agarwal: I totally agree, Jeanny. Now, let's discuss some abstracts related to disparities in the management of patients with genitourinary cancers.  Dr. Jeanny Aragon-Ching: Sure, actually, I would like to discuss 2 abstracts related to disparities in patients with prostate cancer. So the first one, Abstract 265, titled "Patient-Provider Rurality and Outcomes in Older Men with Prostate Cancer." In this study, Dr. Stabellini, Dr. Guha and the team used a SEER Medicare-linked database that included more than 75,000 patients with prostate cancer. The primary outcome was all-cause mortality, with secondary outcomes included prostate cancer-specific mortality. The investigators showed that the all-cause mortality risk was 44% higher in patients with prostate cancer from rural areas who had a provider from a non-metropolitan area compared to those who were in a metropolitan area and had a provider also from a metropolitan area. Dr. Neeraj Agarwal: Those are very important data and highlight the healthcare disparities among the rural population with prostate cancer that still exist.  So what is your key takeaway from Abstract 267, titled "Rural-Urban Disparities in Prostate Cancer Survival," which is a population-based study? Dr. Jeanny Aragon-Ching: Of course. This abstract discusses, actually, a very similar issue regarding access to healthcare among rural versus urban patients. In this study, Dr. Hu and Hashibe and colleagues and team at the Huntsman Cancer Institute assessed all-cause death and prostate cancer-related death risk in a retrospective study in which patients with prostate cancer based on rural versus urban residencies looked at 18,000 patients diagnosed with prostate cancer between 2004 and 2017. 15% lived in rural counties. Similar to the prior abstract we talked about, patients living in rural areas had about a 19% higher risk of all-cause mortality and a 21% higher risk of prostate cancer-specific mortality in comparison to patients living in urban areas. Dr. Neeraj Agarwal: So Jeanny, we can say that both of these abstracts, led by different groups of investigators, highlight that patients with prostate cancer living in rural areas have inferior survival outcomes compared to those living in urban areas, and it is time to focus on the disparities experienced by the rural population with prostate cancer.  Dr. Jeanny Aragon-Ching: Yeah, absolutely Neeraj. I concur with your thoughts.  So, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Yes, before concluding, Jeanny, I want to express my gratitude for your participation and the valuable insights you have shared today. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today.   As we bring this podcast to a close, I would like to highlight the significant advances happening in the treatment of patients with genitourinary cancers during our upcoming 2024 ASCO GU meeting. Many studies featuring practice-impacting data will be presented by investigators from around the globe. I encourage our listeners to not only participate at this event to celebrate these achievements, but to also play a role in disseminating these cutting-edge findings to practitioners worldwide. By doing so, we can collectively maximize the benefit for patients around the world.  And thank you to our listeners for joining us today. You will find links to the abstracts discussed today in 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 very much.  Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guest speakers express their own opinions, experience, and conclusions. Guest statements on the podcast do not necessarily reflect 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  @neerajaiims  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., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

Guest: Dr. Christopher Huerter, Professor and Division Chief Dermatology at Creighton University School of MedicineBreakthrough treatments: Checkpoint inhibitors like Ipilimumab have changed the way we treat melanoma. Now, a new cutting-edge adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has shown promise in metastatic melanoma treatment trials. A new phase III trial compares TIL to Ipilimumab immunotherapy as first- or second-line treatment in patients with advanced melanoma with remarkable results.Article:  https://www.nejm.org/doi/full/10.1056/NEJMoa2210233

Drs Patel, Wright, and Devoe revisit their involvement in the SWOG S1801 trial to highlight available resources that can expand the reach of cancer care in the community oncology setting. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989040). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Malignant Melanoma https://emedicine.medscape.com/article/280245-overview Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma https://www.nejm.org/doi/full/10.1056/NEJMoa2211437 Event-Free Survival https://www.cancer.gov/publications/dictionaries/cancer-terms/def/event-free-survival National Cancer Institute Community Oncology Research Program (NCORP) https://prevention.cancer.gov/major-programs/nci-community-oncology-research-program-ncorp SWOG Cancer Research Network https://www.swog.org/ ECOG-ACRIN Cancer Research Group https://ecog-acrin.org/ NRG Oncology https://www.nrgoncology.org/ Children's Oncology Group https://childrensoncologygroup.org/ Effectiveness of Adjuvant Pembrolizumab vs High-Dose Interferon or Ipilimumab for Quality-of-Life Outcomes in Patients With Resected Melanoma: A Secondary Analysis of the SWOG S1404 Randomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/article-abstract/2798988 Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (MelMarT-II) https://clinicaltrials.gov/study/NCT03860883

Five years, 7 years, or 10 years: How long should follow-up last in melanoma? Dr Sapna Patel and Professor James Larkin discuss the challenges and opportunities. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989039). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Malignant Melanoma https://emedicine.medscape.com/article/280245-overview NCCN Guidelines. Melanoma: Cutaneous https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1492 Malignant Melanoma Staging https://emedicine.medscape.com/article/2007147-overview A Practical Guide to Understanding Kaplan-Meier Curves https://pubmed.ncbi.nlm.nih.gov/20723767/ SWOG Cancer Research Network https://www.swog.org/ Adjuvant Pembrolizumab Versus IFNα2b or Ipilimumab in Resected High-Risk Melanoma https://pubmed.ncbi.nlm.nih.gov/34764195/ Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/34818112/ Estimands — A Basic Element for Clinical Trials https://pubmed.ncbi.nlm.nih.gov/34857075/ Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/36856617/ Definitions of Additional Oncology Drug Endpoints https://www.ncbi.nlm.nih.gov/books/NBK137753/ Adjuvant Nivolumab Versus Ipilimumab in Resected Stage IIIB-C and Stage IV melanoma (CheckMate 238): 4-Year Results From a Multicentre, Double-Blind, Randomised, Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32961119/ Adjuvant Ipilimumab Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (EORTC 18071): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/25840693/ Adjuvant Pembrolizumab Versus Placebo in Resected Stage III Melanoma (EORTC 1325-MG/KEYNOTE-054): Distant Metastasis-Free Survival Results From a Double-Blind, Randomised, Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/33857412/ Pembrolizumab Versus Placebo as Adjuvant Therapy in Completely Resected Stage IIB or IIC Melanoma (KEYNOTE-716): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/35367007/ The Validity of Progression-Free Survival 2 as a Surrogate Trial End Point for Overall Survival https://pubmed.ncbi.nlm.nih.gov/34985773/ Neoadjuvant Talimogene Laherparepvec Plus Surgery Versus Surgery Alone for Resectable Stage IIIB-IVM1a Melanoma: A Randomized, Open-Label, Phase 2 Trial https://pubmed.ncbi.nlm.nih.gov/34608333/

Drs Sapna Patel and Yana Najjar analyze the data and share their approach to frontline therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989035). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134 https://pubmed.ncbi.nlm.nih.gov/36166727/ Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial https://pubmed.ncbi.nlm.nih.gov/36049147/ Long-Term Outcomes of Patients With Active Melanoma Brain Metastases Treated With Combination Nivolumab Plus Ipilimumab (CheckMate 204): Final Results of an Open-Label, Multicentre, Phase 2 Study https://pubmed.ncbi.nlm.nih.gov/34774225/ Health-related Quality of Life With Nivolumab Plus Relatlimab Versus Nivolumab Monotherapy in Patients With Previously Untreated Unresectable or Metastatic Melanoma: RELATIVITY-047 Trial https://pubmed.ncbi.nlm.nih.gov/37167764/ Overall Survival With Combined Nivolumab and Ipilimumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/28889792/ Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial https://pubmed.ncbi.nlm.nih.gov/30811280/ Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915) https://pubmed.ncbi.nlm.nih.gov/36162037/ Single-Agent PD-1 Blockade Is "Treatment of Choice" for Desmoplastic Melanoma https://pubmed.ncbi.nlm.nih.gov/37071762/ Single-agent Pembrolizumab May Benefit Patients With Rare Type of Skin Cancer https://www.aacr.org/about-the-aacr/newsroom/news-releases/single-agent-pembrolizumab-may-benefit-patients-with-rare-type-of-skin-cancer/ Atezolizumab, Vemurafenib, and Cobimetinib as First-Line Treatment for Unresectable Advanced BRAFV600 Mutation-Positive Melanoma (Imspire150): Primary Analysis of the Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32534646/ Overall Survival Benefit With Tebentafusp in Metastatic Uveal Melanoma https://pubmed.ncbi.nlm.nih.gov/34551229/ Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis https://pubmed.ncbi.nlm.nih.gov/28056206/ Single-Agent Anti-PD-1 or Combined With Ipilimumab in Patients With Mucosal Melanoma: An International, Retrospective, Cohort Study https://pubmed.ncbi.nlm.nih.gov/35716907/ CheckMate 067: Long-Term Outcomes in Patients With Mucosal Melanoma. https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.10019 A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab Vs Ipilimumab + Nivolumab In BRAFV600-Mutant Melanoma Brain Metastases https://www.swog.org/clinical-trials/s2000

Drs Sapna Patel and Matteo Carlino dive into the data and consider the current and future roles of adjuvant and neoadjuvant therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989030). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Malignant Melanoma https://emedicine.medscape.com/article/280245-overview Neoadjuvant-adjuvant or Adjuvant-only Pembrolizumab in Advanced Melanoma https://www.nejm.org/doi/10.1056/NEJMoa2211437 Malignant Melanoma Staging https://emedicine.medscape.com/article/2007147-overview Pembrolizumab (Rx) https://reference.medscape.com/drug/keytruda-pembrolizumab-999962 Nivolumab (Rx) https://reference.medscape.com/drug/opdivo-nivolumab-999989 Five-year Analysis of Adjuvant Dabrafenib Plus Trametinib in Stage III Melanoma https://www.nejm.org/doi/10.1056/NEJMoa2005493 Effectiveness of Adjuvant Pembrolizumab vs High-dose Interferon or Ipilimumab for Quality-of-life Outcomes in Patients With Resected Melanoma: A Secondary Analysis of the SWOG S1404 Randomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/36416836/ TNM Classification of Malignant Tumours, 8th Edition https://www.wiley.com/en-gb/TNM+Classification+of+Malignant+Tumours%2C+8th+Edition-p-9781119263579 RECIST 1.1-Update and Clarification: From the RECIST Committee https://pubmed.ncbi.nlm.nih.gov/27189322/ Neoadjuvant Ipilimumab Plus Nivolumab Versus Standard Adjuvant Nivolumab in Macroscopic Stage III Melanoma (NADINA) https://clinicaltrials.gov/ct2/show/NCT04949113 Ipilimumab (Rx) https://reference.medscape.com/drug/yervoy-ipilimumab-999636 An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-risk Melanoma (KEYNOTE-942) https://clinicaltrials.gov/ct2/show/NCT03897881 Adjuvant BRAF-MEK Inhibitors Versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-matched Outcome Analysis https://pubmed.ncbi.nlm.nih.gov/36672358/ Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134 https://pubmed.ncbi.nlm.nih.gov/36166727/

In deze podcast bespreekt internist-oncoloog Koos van der Hoeven recente ontwikkelingen op het gebied van de behandeling van het niet-kleincellig longcarcinoom. Hij bespreekt met longarts Egbert Smit de resultaten van de CheckMate 9LA-studie die hebben geleid tot een nieuwe behandeloptie: eerstelijnsbehandeling van patiënten met gevorderd niet-kleincellig longcarcinoom met nivolumab plus ipilimumab in combinatie met twee cycli chemotherapie versus chemotherapie alleen. Daarnaast worden de PD-L1-expressie en de consequenties voor de behandeling besproken.Referenties 1. Nederlandse richtlijn Niet-kleincellig longcarcinoom. Te raadplegen via richtlijnendatabase.nl/richtlijn/niet_kleincellig_longcarcinoom 2. Hendriks LE, et al. Ann Oncol 2023;34:358-76. 3. Overleving bij stadium IV-NSCLC zonder TKI-gevoelige mutaties (IKNL 2023). Te raadplegen via iknl.nl/kankersoorten/longkanker/registratie/overleving 4. Reck M, et al. J Clin Oncol 2021;39:2339-49. 5. Jassem J, et al. J Thorac Oncol 2021;16:1872-82. 6. Hellmann MD, et al. N Engl J Med 2019;381:2020-31. 7. Paz-Ares L, et al. Lancet Oncol 2021;22:198-211. 8. Reck M, et al. ESMO Open 2021;6:100273. 9. Paz-Ares LG, et al. J Thorac Oncol 2023;18:P204-22. 10. Gandhi L, et al. N Engl J Med 2018;378:2078-92. 11. West H, et al. Lancet Oncol 2019;20:924-37. 12. Samenvatting van de productkenmerken van Opdivo® (nivolumab). Te raadplegen via www.ema.europa.eu/en/documents/product-information/opdivo-epar-product-information_en.pdf 13. Advies van de commissie BOM (2021). Te raadplegen via www.nvmo.org/bom/nivolumab-en-ipilimumab-gecombineerd-met-2-cycli-chemotherapie-als-eerstelijnsbehandeling-voor-gemetastaseerd-niet-kleincellig-longcarcinoom/ 14. Van den Heuvel M, et al. Medische Oncologie 2021.Disclosures Prof. dr. E. Smit: Personal financial interests: none. Institutional financial interests: fees have been paid to my institution for speaker engagements and attendance to advisory boards of AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Bayer, DSI, Eli Lilly, MSD, Merck, Novartis, Pfizer, Sanofi, Takeda, Regeneron, Roche Genentech, Roche Diagnostics. Research support: AstraZeneca, Bristol Myers Squibb, Merck, MSD. PI for clinical studies sponsored by Amgen, AstraZeneca, Bayer, Clovis, Cullingan, Eli Lilly, Merck, MSD, Novartis, PharmaMar, Roche Genentech, Takeda. Prof. dr. ir. J.J.M. van der Hoeven: Astellas, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Gilead, Novartis, medisch directeur van Hartwig Medical Foundation, voorzitter Oncomid, lid Adviescollege VIG en lid RVT DICA. 7356-NL-2300020

Dr. Shannon Westin and her guests, Dr. Michael Atkins, Dr. Adil Daud, and Dr. Gary Schwartz, discuss a definitive work: The DREAMseq Trial. TRANSCRIPT The guests on this podcast episode have no disclosures to declare.     Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast that gets in-depth on articles that have been published in the Journal of Clinical Oncology. And it is my great pleasure to be your host. I'm Shannon Westin, GYN oncology, and I serve as the social media editor for the Journal of Clinical Oncology.   Today, we're going to be discussing a very exciting article describing “The DREAMseq Trial—ECOG-ACRIN EA6134, Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma.” This article was published in the JCO on January 10th, 2023.   And I am joined today by the lead author, Dr. Michael Atkins, who is Deputy Director, Georgetown Lombardi University Hospital, and Scholl Professor and Vice Chair of Oncology at Georgetown University Medical Center. Welcome.   Dr. Michael Atkins: Thank you. Nice to be here.   Dr. Shannon Westin: In addition, we are also accompanied by two experts in the field, Dr. Adil Daud, Professor in the Department of Medicine at the University of California San Francisco, and Director of Melanoma Clinical Research at UCSF Helen Diller Family Comprehensive Cancer Center. Welcome, Dr. Daud.   Dr. Adil Daud: Hi, great to be here.   Dr. Shannon Westin: And with Dr. Daud is Dr. Gary Schwartz, the Division Chief of Hematology Oncology and Deputy Director of the Herbert Irving Comprehensive Cancer Center in Columbia, New York. Thank you for being here.   Dr. Gary Schwartz: Delighted to be here.   Dr. Shannon Westin: So I'm surrounded by experts, and I'm very excited as a GYN oncologist to hear all of what you all have learned in melanoma because we're always excited to take that back into our field. So I think first, though, for those of us that aren't melanoma experts, Dr. Atkins, can you just level set for us and tell us what was the standard of care for melanoma when you began this study?   Dr. Michael Atkins: Sure. Well, first of all, this was a study for patients with BRAF V600 driver mutations in their melanoma, which represents about 50% of the patients with metastatic melanoma. And at the time the study was launched in 2015, two BRAF/MEK inhibitor combinations were FDA approved and shown to produce significant progression-free survival and overall survival benefits relative to BRAF inhibitor monotherapy. In addition, combination checkpoint inhibitor therapy with nivolumab and ipilimumab was shown to be superior to ipilimumab and, in particular in patients with BRAF-mutant melanoma, also to nivolumab monotherapy based on the results of the CheckMate 067 study, leading to its FDA approval. So we had these two regimens there that were approved. Of note, despite the many debates and attempts to garner real-world evidence at the time—the study actually reported out in 2021—marketing data showed that half of all patients in the US with metastatic BRAF-mutant melanoma were receiving BRAF/MEK inhibitors, and only one-quarter received nivo-ipi as initial therapy. So there remained a confusion throughout the course of the study as to which regimen was best in the US and around the world.   Dr. Shannon Westin: Tell me, what led to the current study? Was it really trying to drive at that very question?   Dr. Michael Atkins: These were the best treatment available at the time. And they really had changed melanoma patient outcomes in ways that we could have only dreamed about just five to 10 years prior, when median survival for patients with metastatic melanoma was six to nine months. Hence, the DREAMseq trial, this doublet, randomized evaluation of advanced melanoma sequencing, was really an apt acronym for the trial. But we had these two regimens of BRAF/MEK inhibitors tending to display the overall survival curve, while immunotherapy tended to raise the tail. And at the time the study was launched, it was really unclear which treatment was preferred in general or for particular subsets of patients. And given that patients would likely have the option to receive both approaches, was there a preferred sequence? So the DREAMseq trial was a launch to address these questions.   Dr. Gary Schwartz: I can echo Michael's statement about that. There was also—having been at the beginning of immunotherapy and targeted drug therapy, the transformation of cancer medicine in melanoma was extraordinary. Over a very short amount of time, we transformed a disease that's incurable to curable. And I don't think anybody, at least not in my lifetime, that ever think we'd ever see—or I'd see that type of transformation. But the debate in the community was what should be the first therapy. Should it be a targeted drug combination targeting RAF and MEK for BRAF-mutant melanoma, or should it be immunotherapy? And actually, there was a trend favoring immunotherapy, I think, at the time of the start of the study. It was actually an unresolved issue that many of us were continuing to debate up to the publication of this data, which certainly has now solidified the role of immunotherapy as a starting point for patients with BRAF-mutant melanoma.   Dr. Michael Atkins: Thanks, Gary.   Dr. Shannon Westin: I would love for you—because it is a complex design, and I feel like a lot of times, as drug developers, we're often discouraged to do too many lines in a row. And I was just so intrigued at how well this was laid out to really understand those very questions of superiority as well as sequence, which we don't often assess. Dr. Atkins, will you just summarize the design so that all of the very smart researchers on the line can utilize that for their own cancer types?   Dr. Michael Atkins: Yeah, it was complicated to execute, but the design was pretty simple. Patients with treatment-naive BRAF-mutant metastatic melanoma were stratified according to ECOG performance status and LDH normal and high and randomized in step 1 to receive either combination nivo-ipi induction for 12 weeks, followed by nivo monotherapy maintenance for up to 72 weeks—that was arm A, and that was standard of care for that regimen—or dabrafenib-trametinib continuously, and that was arm B. And if patients experienced disease progression and met the step 2 eligibility criteria, they were able to cross over to the alternative sequence: arm C, dabrafenib-trametinib, or arm D, nivo-ipi. And we followed the patients and chose two-year overall survival as the primary endpoint.   Dr. Shannon Westin: And we kind of got a little hint. So what was the primary finding?   Dr. Michael Atkins: Yes, because of the anticipated distinct shapes of the overall survival curves, with the BRAF/MEK inhibitors tending to have their benefit early and the immunotherapies tending to raise the tail of the curve, we thought there'd be non-proportional hazards and that the overall survival curves might cross. And therefore, we chose as a primary endpoint two-year landmark overall survival, with an estimate that the nivo-ipi first sequence would have a 70% overall survival rate compared to 50% for the dab-tram first sequence. And with 300 patients enrolled and 270 evaluable, there was about a 90% power to show this difference in two-year overall survival rate, with a two-sided type one error rate of 0.05.   Dr. Shannon Westin: And it met its primary endpoint?   Dr. Shannon Westin: Yes, the study was opened in July of 2015, and it was set up that there would be Data Safety Monitoring Committee meetings after the first 100 patients were accrued every six months and that the data cutoff used for the fourth interim Data Safety Monitoring Committee meeting, which was a median follow-up of a little over two years, 265 patients had enrolled in step 1—those were evenly split between the two arms—and 73 had enrolled in step 2, with nearly two-thirds of those being on arm D, second-line nivo/ipi. And the two initial arms were balanced for most of the characteristics and was randomized for the important characteristics.   And from an efficacy standpoint, once again, we chose landmark two-year overall survival as a primary endpoint. And the overall survival curves for the combined sequences showed the anticipated biphasic pattern; they actually crossed around 10 months, and 100 patients had died, with 62 of them on the sequence beginning with dab-tram. And the two-year overall survival rate was 72% for patients who started on nivo/ipi and 52% for those who started on dab-tram. And that was a pretty significant difference; P equals about 0.01 by log-rank test. And so this 95% repeated confidence intervals, along with the 20% difference in overall survival, ranged from 3% to 38%, and the O'Brien-Fleming boundary had been crossed based on this estimate. Interesting, as we published, the three-year overall survival difference was even greater, approaching 24%. So that was the main study endpoint. And because the Data Safety Monitoring Committee felt that that difference was clinically significant even though we had only had about 59% information, they recommended at that point that the study be closed early and that patients who were on arm B, dabrafenib-trametinib, be given the option to cross over to immunotherapy before disease progression.   So that was the primary endpoint. I'm going to pause there. There were some secondary endpoints that I think were interesting, but maybe Gary or Adil have comments about this.   Dr. Shannon Westin: I hope they do, yeah. I'm going to give over my podcast hosting to you.   Dr. Adil Daud: Mike, congratulations on that study. I mean, that's transformative. I mean, I think there was a feeling, like Gary was saying, that immunotherapy might be better in the long term. But I remember a lot of discussions, and I think you answered them in 2015 or 2014 and 2013 because you've been working on this design for a while, that the people who were treated with BRAF inhibitor therapy were just different. And a lot of people would say that when somebody walks into the clinic, the folks who are BRAF-mutant, they just have rapidly progressive disease, like something really bad is going on. And that's why the results on BRAF/MEK inhibitor therapy just looked different than immunotherapy. Immunotherapy was for slower-growing tumors, and I think your study kind of puts maybe a different spin on that, basically suggesting differently. Would you comment on that?   Dr. Michael Atkins: Yeah. So, Adil, I think early on, people thought that the BRAF/MEK inhibitor was for patients who had rapidly progressive disease, and you needed to get a response to get the disease under control. But over time, as those studies were followed out, it appeared that the BRAF/MEK inhibitors tended to work best in patients who had less aggressive disease—performance status 0, M1a or b disease, and normal LDH. And so it was still confusing as to who should get which therapies. And when you compared the results using retrospective data between those who got immunotherapy and those who got targeted therapy, it was really difficult to be sure that these were the same patient population. So the only way you could really know whether immunotherapy was truly better was to do prospectively randomized studies where the two arms were balanced, which is what we set out to do in DREAMseq.   Dr. Adil Daud: Yeah, I think there's a lot of areas in oncology where people think whether you should give somebody a CAR T-cell or whether you should give somebody myeloma therapy or—people think, well, these are just totally different. Or in melanoma, I think, the TIL therapy, there's this question about, can you really compare that to anything else? And I think your study, which perhaps wouldn't be done by a pharmaceutical company and perhaps wouldn't be— outside of the cooperative groups, I feel that it's hard to really do a study of that type.   Dr. Michael Atkins: I agree.   Dr. Gary Schwartz: Yeah. First, I want to say congratulations on really an extraordinary study, Michael. I think it really answers some critical clinical and biological questions that have been subject to debate in the melanoma and the medical oncology community for the last five or more years.   There were a couple of things that surprised me. One was the fact that patients that started on dab-trame, when crossed over to immunotherapy, the outcomes were pretty poor. And that was a biological outcome, I guess, we kind of thought about. But this study certainly suggests that there's something about prior targeted drug therapy that may affect outcome and immunotherapy. And also, the other thing that was surprising was the number of dropouts that developed and couldn't cross over because of the rapid progression on the first-line study. Do you want to comment on both of those points and maybe share some thoughts about what that means for the medical care of patients who get this type of treatment?   Dr. Michael Atkins: Sure. First of all, response rates were similar between the step 1 regimen and for dab-tram, whether used in step 1 or step 2. In contrast, as you said, nivo-ipi appeared to be less effective after progression on dab-tram than in the first line. It was like a 46% response rate in the first line, and about 30% in the second line. The median PFS in the first line was about 11+ months, and in the second line, was only about three months. And I think there was some feeling in the community—probably wishful thinking and also based on what I think are some flawed preclinical and translational studies—that BRAF/MEK inhibitors might cause some immunogenic cell death and cause new antigens to be expressed and activate the immune system, be synergistic with immunotherapy given afterwards, while I think other data suggested that the resistance mechanism to the dabrafenib-trametinib was immunosuppressive, leading to upregulation of VEGF and things like that.   So this result suggested that immunotherapy didn't work as well in the second line. There are probably several reasons for that. It could be biologic changes, which I think we don't pay enough attention to when we think about what we're doing in the first and the second line. But also the type of patients who progressed on BRAF/MEK inhibitors. when you stop those drugs, the disease tends to accelerate. Many of them probably had subclinical CNS disease, and it was just not a good time for them to be going on immunotherapy, while in the front line, you didn't have to deal with those type of issues. And with regard to crossover, one of the things that we looked at as a secondary endpoint in this study was feasibility of doing the crossover. Because in clinical practice, we found that if you waited until disease progression on BRAF/MEK inhibitors and then tried to cross them over, oftentimes, patients progressed really rapidly, and you weren't able to get the immunotherapy in to large degree, while in patients who got immunotherapy, they had a lot of toxicity often, which caused them to stop therapy. And if they had toxicity at the time they were progressing, it might be complicated to add new drugs in.   And so I think the community was a bit surprised that only about half the patients were able to successfully cross over. But I think that's reality, that if you use these drugs to progression and then have eligibility criteria, which you have to have in a clinical trial for patients to go on the second-line treatment, you're going to have a lot of dropouts. One of the major reasons for dropouts on dab-tram was progression in the CNS, and dabrafenib-trametinib doesn't work as well in the CNS as it does systemically, while immune therapy actually appears to work as well for patients with asymptomatic or undetected CNS metastases as it does systemically. And I think that was an important reason why immunotherapy was better.   Dr. Gary Schwartz: I've looked at your paper now multiple times, Michael, and I can't think of any reason why anybody would want to start a targeted therapy for BRAF-mutant melanoma. I mean, I think this really becomes a definitive study declaring that immunotherapy is where all medical oncology should begin in the treatment of BRAF metastatic melanoma. Is that too much of a statement to make, or would you agree with that as well? I've been trying to think of all the reasons why not to give immunotherapy first. I can't think of one now, after your paper, that would suggest otherwise.   Dr. Michael Atkins: Well, I've been chastened by a lot of reviewers, as you know, to say that these results only definitively apply to the patients who were eligible for this study. And patients who had poor performance status or active brain mets or who required steroids and needed to be in the hospital or had to have a response were not eligible for this study. And so I think there are some patients where the disease is just on fire, where you may need to give BRAF/MEK inhibitors to try to cool it off before you start immunotherapy, particularly if patients need to be on immunosuppressive drugs to control edema in their brain, or because of bone mets pressing on the spinal cord or things like that, I think that it's important to have that other option. But as soon as you can, as soon as you've created enough window to get patients off immunosuppressive drugs or improve their performance status enough so that they can be an outpatient, you probably should switch to immunotherapy and give them the chance for a long-term benefit.   Dr. Adil Daud: I have doctors call me outside of academia and say, “Hey, I've got a patient walking in. I'm trying to decide, should I do the triple therapy, or should I do…”—which triple therapy in melanoma refers to dabrafenib plus trametinib plus a PD-1 drug like pembrolizumab or, in some cases, like a PDL-1 inhibitor—and they're questioning whether that's an appropriate place to start. Or sometimes people say, “Well, what about doing a sandwich regimen where we start off with dabrafenib-trametinib and then switch over to something else without waiting for progression just to give people…” And I give a long-winded answer to that, but I'm curious to hear what you think, what you both think.   Dr. Michael Atkins: So my view is—I've always thought, based on some of our early translational studies, which were presented at ASCO and hopefully we'll be able to publish soon, that the BRAF/MEK inhibitor data that showed that there was an influx of immune cells and potential synergy was actually an artifact, that it was not increasing immune cells in the tumor microenvironment, but actually loss of tumor cell in the tumor microenvironment that was causing the impression that the tumors were more inflamed. And I felt that when it came to immunotherapy, BRAF/MEK inhibitors were not ipilimumab and were not going to add to the benefit that we see with immunotherapy of durable responses the way you can see with nivo/ipi.   So I've stayed away from those triplet regimens, and I think we've seen with the studies that have been published so far that they tend to have sub-additive benefit when you add an anti-PD-1 to BRAF/MEK inhibitors. You see some prolongation of PFS, but you don't see the same tail of the survival curve. And even at two years, the tail of the survival curve for those triple regimens is below where it is for nivo/ipi in the BRAF-mutant population all the way out at five years. And the nivo/ipi population—I'm talking about the progression-free survival curve—and that nivo/ipi population can still get BRAF/MEK inhibitors if they progress. So I think that triple regimen, I can't think of a patient where I would use that. But the sandwich regimen, as I was just describing, may be useful in some patients who just aren't in appropriate shape to start with immunotherapy.   Dr. Gary Schwartz: Now, I would agree with Michael. I think the clinical trial data would really discourage the use of triplet therapy. They really lean—again, the benefit of triplet therapy for all the published papers we've seen so far in that area. But I guess you're right. The idea, if you have one of those patients that comes in and who's really on fire with rapidly progressive disease, on steroids, and needs a very quick benefit, perhaps initiating targeted therapy first for a short time would be reasonable in the treatment of those patients. But beyond that, I really think there probably are not going to be many exceptions to starting immunotherapy first because your data, to me, strongly would suggest that starting targeted therapy is going to diminish the benefits of immunotherapy to follow. And that, to me, is an important take-home point of the study and sort of validates some of the preclinical data. I mean, depends what you look at. But there is preclinical data suggesting that MEK inhibition will diminish T-cell responsiveness, and I think this supports that biological effect. So I think we have to be cautious about upfront targeted drug therapy now and have to find what are those opportunities where it may be appropriate. But I think they're really diminishingly few.   Dr. Michael Atkins: And I would just emphasize the flip side of that, which is that targeted therapy is equally effective in the second line for patients who don't respond to immunotherapy. And I think that was also a critical component of why the immunotherapy first sequence was better than the targeted therapy first sequences. You had better salvage.   Dr. Gary Schwartz: That's a very good point.   Dr. Shannon Westin: Well, I personally just want to thank the three of you. I learned a ton today, and I fully intend to take that back to the work that we're doing in gynecologic malignancies, combining immune therapies and targeted therapies, and I hope our listeners will do the same.   Further, I agree with you, Dr. Schwartz. I think this is a practice-changing study. I appreciate you, Dr. Atkins, in being a little cautious. I appreciate the editors that reviewed it as well. But this is as clear a definitive trial as we can get and a testament to your hard work through the cooperative groups, which we all know can be a struggle in itself to get this type of trial through. So congratulations again.   Dr. Gary Schwartz: And I think the lessons learned in melanoma are going to be applicable to all solid tumors. So melanoma is about so far ahead of many other tumors, but what we learned here isn't just impacting melanoma, but will impact all cancer medicine. And I think that what's so important about this trial is that lessons learned here really are broadly based and have clinical applications to many patients getting immunotherapy, targeted drug therapies today. So congratulations, Dr. Atkins. I think you hit a home run on this one. The medical oncology community is indebted to you and to your group to making this possible. And thank you for bringing it to JCO as well. I think that itself speaks to the success of the journal and the impact these types of studies have on reaching a large segment of the medical oncology community.   Dr. Michael Atkins: Well, thank you very much, Gary. I do want to emphasize the point you made, that I think this result does impact how we think about the use of targeted therapies or chemotherapies or antiangiogenic therapies in other tumors in coordination with immunotherapy. And I'm sort of on a mission to make the point that if you want to get the most benefit out of immunotherapy, you should give it first, and you should give it unencumbered by other things that might interfere with its activity.   Dr. Gary Schwartz: I think that's the last word, Shannon.   Dr. Shannon Westin: I believe it is. I believe it is. Thank you all so much for being here. And thank you to our listeners for being here for another episode of JCO After Hours. Again, we were discussing “Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial—ECOG-ACRIN EA6134,” published in January 10th, 2023, in the JCO.   Please do check out our other podcast offerings. You can check them out on the JCO website or anywhere you get your podcasts. Until next time, be well.     The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

What is the relationship between gut microbiome and depressive symptoms?

David McDermott and Brian Rini debate this topic.

Drs Sumanta Pal and Rana McKay discuss the use of biomarkers in treating patients with renal cell carcinoma to identify whose disease will recur and who will respond to therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968743). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma https://ascopubs.org/doi/10.1200/JCO.22.00219 The Detection of EpCAM+ and EpCAM­– Circulating Tumor Cells https://www.nature.com/articles/srep12270 Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768333/ ctDNA Guiding Adjuvant Immunotherapy in Urothelial Carcinoma https://www.nature.com/articles/s41586-021-03642-9 Clinical Activity and Molecular Correlates of Response to Atezolizumab Alone or in Combination With Bevacizumab Versus Sunitinib in Renal Cell Carcinoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721896/ Atezolizumab Plus Bevacizumab Versus Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (IMmotion151): A Multicentre, Open-Label, Phase 3, Randomised Controlled Trial https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(19)30723-8 Nivolumab Plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/nejmoa1712126 Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study https://clinicaltrials.gov/ct2/show/NCT05361720 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 Single-Cell RNA Sequencing of Human Kidney https://www.nature.com/articles/s41597-019-0351-8 Progressive Immune Dysfunction With Advancing Disease Stage in Renal Cell Carcinoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138872/

Drs Sumanta Pal and Jennifer Wargo discuss how the gut microbiome impacts response to cancer therapy in patients with renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968742). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Gut Microbiome Modulates Response to Anti-PD-1 Immunotherapy in Melanoma Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827966/ The Microbiome in Cancer Immunotherapy: Diagnostic Tools and Therapeutic Strategies https://pubmed.ncbi.nlm.nih.gov/29567708/ Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Anti-PD-L1 Efficacy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873287/ Anticancer Immunotherapy by CTLA-4 Blockade Relies on the Gut Microbiota https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721659/ Gut Microbiome Influences Efficacy of PD-1-Based Immunotherapy Against Epithelial Tumors https://pubmed.ncbi.nlm.nih.gov/29097494/ Dietary Fiber and Probiotics Influence the Gut Microbiome and Melanoma Immunotherapy Response https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970537/ Fiber in Diet Linked to Cancer Immunotherapy Response https://www.nih.gov/news-events/nih-research-matters/fiber-diet-linked-cancer-immunotherapy-response Fecal Microbiota Transplant Promotes Response in Immunotherapy-Refractory Melanoma Patients https://www.science.org/doi/10.1126/science.abb5920 Fecal Microbiota Transplant Overcomes Resistance to Anti-PD-1 Therapy in Melanoma Patients https://pubmed.ncbi.nlm.nih.gov/33542131/ Fecal Microbiota for Transplantation: Safety Alert - Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission Fecal Microbiota Transplantation Followed by Anti–PD-1 Treatment in Patients With Advanced Melanoma https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.9533 Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma https://clinicaltrials.gov/ct2/show/NCT04940299 Nivolumab plus Ipilimumab With or Without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018425/

CME credits: 0.75 Valid until: 30-09-2023 Claim your CME credit at https://reachmd.com/programs/cme/adjuvant-nivolumab-alone-or-in-combination-with-ipilimumab-versus-placebo-in-stage-iv-melanoma-with-no-evidence-of-disease-overall-survival-results-of-immuned-a-randomized-double-blind-multi-center-phase-2p-decog-trial/14451/ tbd

Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019 An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1 Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180 International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31 Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716 The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706 Twitter poll questions: What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877 What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305 What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057 Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/ OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf

In this episode, Sandip Patel, MD shares his thoughts on optimizing immune checkpoint inhibitor (ICI) therapy in advanced non-small-cell lung cancer (NSCLC) and discusses best practices for individualizing therapy decisions and managing adverse events.Topics include:Currently approved ICIsRole of biomarker and PD-L1 testing in advanced NSCLCStrategies to individualize ICI treatment for patients with advanced NSCLCStrategies for identifying and managing immune-related adverse events in patients treated with ICIPresenter:Sandip P. Patel, MDAssociate ProfessorDepartment of MedicineDivision of Hematology/OncologyUniversity of California – San DiegoLa Jolla, California Link to full program:https://bit.ly/39vuCHC

In this episode, Beth Sandy, MSN, CRNP provides her thoughts on key data presented at the 2022 ASCO annual conference relating to immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). Findings covered include:Survival results after 3 years from the phase III Checkmate 9LA study of nivolumab and ipilimumab combined with 2 cycles of chemotherapy vs chemotherapy in previously untreated advanced NSCLCUpdated survival and safety results after 5 years from the phase III Checkmate 227 study of nivolumab and ipilimumab vs chemotherapy in previously untreated advanced NSCLC, including assessment of a treatment-free intervalUpdated analysis from the phase III ATEZO-BRAIN trial of atezolizumab + carboplatin and pemetrexed in patients with advanced NSCLC with untreated brain metastases Updated overall response analysis from the phase II KEYNOTE-799 study of pembrolizumab with concurrent chemoradiation in unresectable, locally advanced stage III NSCLCResults from a phase II trial evaluating nivolumab plus ipilimumab vs nivolumab monotherapy following chemoradiation in unresectable stage III NSCLCPathological complete response results from the phase II NADIM II study of nivolumab and chemotherapy vs chemotherapy in the neoadjuvant NSCLC settingPresenter:Beth Sandy, MSN, CRNPNurse PractitionerAbramson Cancer CenterUniversity of PennsylvaniaPhiladelphia, PennsylvaniaLink to full program:https://bit.ly/39vuCHC

Cancer drugs have rapidly evolved in the last decade. Alongside the significant benefits are new toxicity profiles that clinicians need to be aware of and manage.In this podcast, A/Prof Carlino interviews fellow Medical Oncologist Prof Georgina Long AO on the adverse events/toxicities associated with targeted therapies (combination BRAF/MEK inhibitors) and immunotherapies (anti-PD-1, anti-LAG-3 and anti-CTLA-4), particularly in melanoma, and how they should be managed.Some key points brought up during this deep dive in toxicity:With targeted therapies, cessation of treatment usually reverses the toxicity.Immunotherapy toxicities are driven by the immune system rather than the drugs themselves, and as such, cessation of treatment does not automatically resolve toxicity. Most toxicities need active treatment to resolve.It is crucial to educate your patients regarding temporarily ceasing therapy in response to toxicity, particularly fever.It is important to recognise that immunotherapy toxicity is not necessarily treated the same as the autoimmune disease it may mimic.Understanding the patient's history is crucial to identify if symptoms are a direct result of treatment.Ceasing immunotherapy treatment in the setting of toxicities does not mean you lose efficacy.It is important to understand the risk versus benefit when assessing your patient for re-challenge with immunotherapy after a toxicity.Medical Oncologists should have a referral network of experts for managing your patient's toxicities.This podcast is suitable for Oncologists, Emergency Medicine Physicians, GPs, Oncology Nurses and other healthcare professionals.SPEAKERSProf Georgina Long AO - Co-Medical Director, Melanoma Institute Australia | Chair, Melanoma Medical Oncology and Translational Research, Melanoma Institute Australia and Royal North Shore Hospital, The University of SydneyA/Prof Matteo Carlino - Medical Oncologist, Melanoma Institute Australia, Westmead and Blacktown Hospitals Clinical Associate Professor, The University of SydneyPlease note that this podcast was accurate at the time of recording (May 2022) but may not reflect the rapidly evolving treatment landscape and approvals in Australia.MIA's Education Program is proudly supported through unrestricted educational grants from: MSD, Bristol Myers Squibb, Novartis and HEINE.

Yelena Janjigian describes ipi/nivo vs nivo chemo vs chemo in Gastric cancer - published in Nature

In this first episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss the latest data supporting their approach to selecting treatment regimens for patients with HCC, with topics including: the current challenges in the management of HCC, recommended initial workup strategies and the evolving treatment landscape in HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this second episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss how to identify, prevent and mitigate treatment-related adverse events, and review cases with careful considerations for patient-specific factors guiding treatment selection, followed by a question-and-answer session on the management of patients with HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this podcast episode, Sarah M. Tinsley, PhD, APRN, AOCN, discusses management strategies for secondary AML and novel therapies currently in clinical trials for AML. Topics include:Liposomal cytarabine plus daunorubicin for secondary AMLAn overview of emerging immune-based strategies for AMLEvidence on immune-based therapies, including agents targeting CD47, TIM3, and bispecific antibodiesPresenter:Sarah M. Tinsley, PhD, APRN, AOCNNurse PractitionerCourtesy Assistant ProfessorDepartment of Malignant HematologyMoffitt Cancer CenterUniversity of South FloridaTampa, Florida 

David McDermott describes his Clinical Cancer Research paper on this topic.

In this podcast episode, Julie Brahmer, MD, MSc, and Jarushka Naidoo, MB BCH BAO, MHS, answer audience questions from a live CCO webinar on evolving immunotherapy strategies for NSCLC, with topics including:Patient and/or disease-related factors considered when choosing first-line immunotherapy-based regimensSecond-line therapeutic options after disease progression on an immunotherapy-based regimenImmunotherapy in patients with advanced NSCLC and brain metastasesDistinguishing between immunotherapy-induced and radiation-induced pneumonitis, with expert perspective on rebiopsyFuture directions in immunotherapy for NSCLC, including the role of the gut microbiome in responsePresenters:Julie Brahmer, MD, MScProfessor of OncologyDirector, Thoracic OncologyCo-Director, Upper Aerodigestive Cancer ProgramBloomberg-Kimmel Institute for Cancer ImmunologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins MedicineBaltimore, MarylandJarushka Naidoo, MB BCH BAO, MHSConsultant Medical OncologistBeaumont Hospital/RCSI University of Health SciencesDublin, IrelandAdjunct Assistant Professor of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins UniversityBaltimore, MarylandContent based on an online CME program supported by educational grants from Bristol-Myers Squibb; Genentech, a member of the Roche Group; Helsinn Healthcare SA; and Merck Sharp & Dohme Corp.Link to full program:https://bit.ly/3CLC0Hd

Mike Atkins discusses the role of CTLA4 inhibition in RCC.

In this podcast episode, Jeffrey S. Weber, MD, PhD; Allison Betof Warner, MD, PhD; and Hussein Tawbi, MD, PhD, discuss recent key data on adjuvant and neoadjuvant therapy and review the latest evidence on therapies for metastatic disease.Link to full program:https://bit.ly/3ogPjMoFollow along with the downloadable slideset:https://bit.ly/2XYNIztPresenters:  Jeffrey S. Weber, MD, PhDDeputy DirectorLaura and Isaac Perlmutter Cancer CenterNYU Langone HealthProfessor of MedicineNYU Grossman School of MedicineNew York, New YorkAllison Betof Warner, MD, PhDAssistant MemberAssistant Attending PhysicianMelanoma ServiceDivision of Solid Tumor OncologyDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New YorkHussein Tawbi, MD, PhDProfessorDepartment of Melanoma Medical OncologyThe University of Texas MD Anderson Cancer CenterHouston, Texas 

The Oncology Journal Club - Delivering Oncology News DifferentlyThe Oncology Podcast, brought to you by Oncology News Australia, is proud to present Episode 47 in our series The Oncology Journal Club.This week Eva Segelov talks us through a practice changing paper on the duration of adjuvant aromatase-inhibitor therapy in postmenopausal breast cancer. Craig Underhill looks at the KEYNOTE-598 study on metastatic non-small-cell lung cancer aaaaand Hans Prenen is back! He tackles the therapeutic implications of germline testing in advanced cancers.Quick bites are as diverse as ever covering the NeoSCOPE trial, text messaging, cancer misinformation and fake news, conflicts of interest, liquid biopsies and much more.As ever, you'll find links to all the papers, bios and twitter handles in the notes on our website.With the usual top quality banter, papers you won't hear of anywhere else and expert analysis from our Hosts, you are in for another great episode of The Oncology Journal Club!Full bios and the list of all papers discussed are available on our website.For the latest oncology news visit www.oncologynews.com.au and for regular oncology updates for healthcare professionals, subscribe for free to get the weekly The Oncology Newsletter.The Oncology Podcast - An Australian Oncology Perspective

Gunhild von Amsberg und Markus Graefen diskutieren die Studie und sprechen über mögliche Biomarker, insbesondere auch zur besseren Patientenselektion für eine Immuntherapie. Sie streifen neue molekularpathologische und immuntherapeutische Konzepte und geben einen Ausblick auf die aktuell in Entwicklung befindlichen zielgerichteten Immuntherapien mit BiTES und CAR-T-Zellen.

In this episode, David Kaplan, MD, MSc, and Thomas Karasic, MD, review approved immunotherapy options for advanced HCC and answer key questions surrounding use of immune checkpoint inhibitors, with topics including:Current systemic therapy standards of care for patients with advanced HCCUse of single-agent immune checkpoint inhibitor therapy in the first-line settingAssessing bleeding riskUsing immunotherapy in patients with active HBV or HCV infectionsPresenters:David Kaplan, MD, MScAssociate ProfessorPerelman School of MedicineUniversity of PennsylvaniaDirector of HepatologyCorporal Michael J. Crescenz VA Medical CenterPhiladelphia, PennsylvaniaThomas Karasic, MD  Assistant Professor of MedicineDepartment of Hematology-OncologyUniversity of PennsylvaniaPhiladelphia, Pennsylvania Content based on an online CME program supported by an educational grant from Genentech, a member of the Roche Group.Link to full program:https://bit.ly/39V6s72

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

In this episode, Amit G. Singal, MD, MS, and Lipika Goyal, MD, discuss key considerations key considerations for hepatologists, oncologists, and other healthcare professionals in the contemporary use of immune checkpoint inhibitors for treating specific case patients with advanced hepatocellular carcinoma, including:First-line systemic treatment for a patient with Child-Pugh A liver function and no elevated bleeding riskFirst-line systemic treatment for a patient with Child-Pugh A liver function and elevated bleeding riskFirst-line systemic treatment for a patient with Child-Pugh B liver functionSecond-line systemic treatment for a patient previously receiving atezolizumab plus bevacizumabManagement of immune-mediated hepatitis in a patient with HBV receiving an immune checkpoint inhibitorPresenters:Amit G. Singal, MD, MSChief of HepatologyMedical Director, Liver Tumor ProgramProfessor, Department of Internal MedicineUT Southwestern Medical CenterDallas, TexasLipika Goyal, MDLead of the Liver Cancer Research ProgramAssistant Professor of MedicineHarvard Medical SchoolMassachusetts General Hospital Cancer CenterBoston, MassachusettsContent based on an online CME program supported by an educational grant from Genentech, a member of the Roche Group.Link to full program:https://bit.ly/39V6s72

In this episode, José Ignacio Nolazco, MD, and Alejandro Nolazco, MD, discuss in Spanish the latest immuno-oncology developments in the treatment of urothelial cancer from an Argentinian perspective.  Presenters:José Ignacio Nolazco, MD  Urology FollowHospital Universitario AustralBuenos Aires, ArgentinaAlejandro Nolazco, MDAssociate ProfessorDepartment of UrologyUniversidad Austral and Universidad Católica ArgentinaBuenos Aires, ArgentinaContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program, including associated downloadable slidesets and on-demand Webcast:https://bit.ly/3kJC5SL 

Link to CME: Claim CreditIn this episode, Amit G. Singal, MD, MS, and Lipika Goyal, MD, discuss key considerations in the contemporary use of immune checkpoint inhibitors for treating patients with advanced hepatocellular carcinoma, with topics including:Optimal use of the newly approved immune checkpoint inhibitor/VEGF inhibitor combination of atezolizumab plus bevacizumabUse of nivolumab ± ipilimumab and pembrolizumabEmerging immunotherapy combinations currently being investigated in clinical trialsManagement of key adverse events with immune checkpoint inhibitorsPresenters:Amit G. Singal, MD, MSChief of HepatologyMedical Director, Liver Tumor ProgramProfessor, Department of Internal MedicineUT Southwestern Medical CenterDallas, TexasLipika Goyal, MDLead of the Liver Cancer Research ProgramAssistant Professor of MedicineHarvard Medical SchoolMassachusetts General Hospital Cancer CenterBoston, MassachusettsContent based on an online CME program supported by an educational grant from Genentech, a member of the Roche Group.Link to full program:http://bit.ly/39V6s72

Pr Pierre Bigot : Highlights des recommandations CCAFU 2020-2022 du cancer du reinQuelles sont les messages clés des nouvelles recommandations ? Quelles sont les nouveautés dans la prise en charge chirurgicale du cancer du rein métastatique ? Quelles sont les nouveautés dans le traitement médical de première ligne du cancer du rein métastatique ? Quels messages retenir pour les tumeurs kystiques et les angiomyolipomes sporadiques ?Le Pr Pierre Bigot (CHU d’Angers) répond à toutes vos questions !L’orateur n’a pas reçu de rémunération pour la réalisation de cet épisode.Cet épisode a été réalise grâce au soutien institutionnel des laboratoires IPSENPour aller plus loin :Recommandations françaises du Comité de Cancérologie de l’AFU : actualisation 2020-2022 : prise en charge du cancer du reinhttps://purol-12s.elsevierdigitaledition.com/2/https://www.urofrance.org/outils-et-recommandations/recommandations/recommandations-afu/classees-par-annee.htmlÉtude Carmena :Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Beisland C, Aitchison M, Oudard S, Patard JJ, Theodore C, Chevreau C, Laguerre B, Hubert J, Gross-Goupil M, Bernhard JC, Albiges L, Timsit MO, Lebret T, Escudier B. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018 Aug 2;379(5):417-427. doi: 10.1056/NEJMoa1803675. Epub 2018 Jun 3. PMID: 29860937.Etude SURTIME :Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, van Velthoven R, Del Pilar Laguna M, Wood L, van Melick HHE, Aarts MJ, Lattouf JB, Powles T, de Jong Md PhD IJ, Rottey S, Tombal B, Marreaud S, Collette S, Collette L, Haanen J. Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):164-170. doi: 10.1001/jamaoncol.2018.5543. Erratum in: JAMA Oncol. 2019 Feb 1;5(2):271. PMID: 30543350; PMCID: PMC6439568.Keynote 426 :Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang YH, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T; KEYNOTE-426 Investigators. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16. PMID: 30779529. Checkmate 214 :Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21. PMID: 29562145; PMCID: PMC5972549. Cet épisode a été réalisé grâce au soutien institutionnel des laboratoires IPSEN.Musique du générique : Via AudioNetworkResponsable projet

Link to CME: Claim CreditIn this episode, Amit G. Singal, MD, MS, and Lipika Goyal, MD, answer clinician questions on current best practices and emerging applications  with immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma, with topics including:Optimal use of the newly approved immune checkpoint inhibitor/VEGF inhibitor combination of atezolizumab plus bevacizumabUse of immune checkpoint inhibitor therapy in patients with Child-Pugh B liver functionUse of biomarkers to inform treatment for patients with advanced HCCPresenters:Amit G. Singal, MD, MSChief of HepatologyMedical Director, Liver Tumor ProgramProfessor, Department of Internal MedicineUT Southwestern Medical CenterDallas, TexasLipika Goyal, MDLead of the Liver Cancer Research ProgramAssistant Professor of MedicineHarvard Medical SchoolMassachusetts General Hospital Cancer CenterBoston, MassachusettsContent based on an online CME program supported by an educational grant from Genentech, a member of the Roche Group.Link to full program:https://bit.ly/39V6s72

呼吸科星期二 2020年11月3日 第2集FDA 免疫检查点抑制剂进入肺癌的一线治疗NEJM 治疗耐药结核时，短疗程方案不劣于长疗程方案Cell CT的人工智能系统可用于诊断COVID-19德瓦鲁单抗（durvalumab）德瓦鲁单抗是一种PD-L1单抗，此前已被批准用于治疗晚期膀胱癌和无法切除的3期非小细胞肺癌。2020年3月，德瓦鲁单抗被批准用于广泛期小细胞肺癌联合标准化疗的一线用药。《CASPIAN研究：德瓦鲁单抗联合铂-依托泊苷治疗广泛期小细胞肺癌的疗效》Lancet，2019年11月 (1)这项研究的目的是评估德瓦鲁单抗与依托泊苷联合顺铂或卡铂治疗广泛期小细胞肺癌的疗效，对照组方案是依托泊苷联合顺铂或卡铂。这项随机、开放标签、三期试验，纳入未经治疗的、广泛期小细胞肺癌患者537人，随机分为德瓦鲁单抗+铂/依托泊苷组、铂/依托泊苷组。联合德瓦鲁单抗组总生存率显著改善，优势比为0·73（p = 0·0047）。联合德瓦鲁单抗组和不使用德瓦鲁单抗组中，中位总生存期分别为13·0个月和10·3个月；随访至18个月时，两组分别有34%和25%的患者存活。结论：一线德瓦鲁单抗联合铂/依托泊苷显著改善广泛期小细胞肺癌患者的总生存率。纳武利尤单抗+ 伊匹木单抗（nivolumab+ipilimumab）2020年5月，FDA批准纳武利尤单抗（抗PD-1单抗）和伊匹木单抗（CTLA-4单抗），两个药物联合低剂量化疗作为转移或复发的非小细胞肺癌的一线治疗方案。《CheckMate 227研究：纳武利尤单抗联合伊匹木单抗治疗晚期非小细胞肺癌的3期临床研究》New England of Medicine，2019年11月 (2)此项开放标签的3期临床研究的目的是，评价晚期非小细胞肺癌患者中使用PD-1单抗（纳武利尤单抗）+CTLA-4单抗（伊匹木单抗）联合治疗的长期获益。研究纳入PD-L1表达水平≥1%的、Ⅳ期或复发的、非小细胞肺癌患者，随机分入纳武利尤单抗+伊匹木单抗双联治疗组、或纳武利尤单抗单药治疗、或化疗组；同时也纳入了PD-L1表达水平＜1%的患者，随机分三组中。所有患者之前均未接受过化疗。在PD-L1表达水平≥1%的患者中，纳武利尤单抗+伊匹木单抗组和化疗组的中位总生存期分别为17.1个月和14.9个月（P=0.007），2年总生存率分别为40.0%和32.8%，中位缓解时间分别为23.2个月和6.2个月。在PD-L1表达水平＜1%的患者中也观察到了总生存期获益，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.2个月和12.2个月。全部患者中，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.1个月和13.9个月，严重不良事件发病率分别为32.8%和36.0%。结论：在非小细胞肺癌患者中，纳武利尤单抗+伊匹木单抗一线治疗组的总生存期超过化疗组，且与PD-L1表达水平无关。长期随访中未发现新的安全性问题。阻塞性睡眠呼吸暂停阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）是一种因睡眠过程中上气道反复塌陷引起的、以阻塞性呼吸暂停和低通气为特征的疾病。对于存在白天睡眠过多、打鼾和睡眠中窒息或倒吸气等症状的、高龄、肥胖、男性患者，应该考虑这个诊断。多导睡眠监测图是诊断的金标准，诊断标准为：无相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥15次/小时；伴有相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥5次/小时。相关症状包括：嗜睡、疲劳、失眠，觉醒时存在憋气、倒吸气或窒息，或者观察者发现患者习惯性打鼾、呼吸中断。相关疾病包括：高血压、心境障碍、认知功能障碍、冠心病、脑卒中、心力衰竭、心房颤动或2型糖尿病。《前瞻性研究：睡眠呼吸障碍和失眠与高血压和糖尿病的关系》American Journal of Respiratory and Critical Care Medicine，2020年7月 (3)这项前瞻性研究，通过长达6年的随访，旨在调查美国西班牙裔/拉丁裔人群中，睡眠呼吸障碍和失眠与高血压和糖尿病发生之间的关联，共纳入11623名参与者，女性占52.6％，平均年龄41.1±14.9岁。存在睡眠呼吸障碍的人群，与没有睡眠呼吸障碍的人群比较，高血压发生的风险比1.54，糖尿病发生风险比1.37。失眠与高血压有关（风险比1.37），其中男性关联性更强。结论：睡眠呼吸障碍与高血压和糖尿病有关。失眠与高血压有关。这些结果支持将睡眠障碍作为预防和减少高血压、糖尿病的靶标。《SAVE研究：持续气道正压治疗对同时患有OSA和稳定性冠心病的患者的糖尿病的影响》Diabetes Care，2020年7月 (4)研究试图确定在同时患有稳定性冠心病和OSA患者中，长期持续气道正压（CPAP）通气治疗对血糖控制和糖尿病风险的影响。研究收集了888名同时患有稳定性冠心病和OSA患者，一组接受CPAP加常规治疗，另一组接受常规治疗，中位随访时间为4.3年。糖尿病的患者中，不同治疗组的血糖、糖化血红蛋白或降糖药物使用方面无显著差异。糖尿病前期、或新诊断的糖尿病患者中，组间也没有显著差异。有趣的是，女性糖尿病患者在常规治疗组表现较差，而接受CPAP治疗后病情更稳定。结论：在同时患有稳定性冠心病和OSA患者中，尚无证据证明长期CPAP治疗对血糖控制有益。但研究中发现的性别差异仍需进一步验证。阻塞性睡眠呼吸暂停的治疗一般治疗包括：减重、运动、侧卧位睡眠、避免酒精、避免使用精神类药物。主要治疗方法是气道正压治疗，常见模式包括持续气道正压（CPAP）、双水平气道正压（BPAP）和自动调定式的气道正压（APAP），最常用的是CPAP。替代治疗方法包括：轻中度患者可尝试口腔矫正器、存在上气道阻塞的患者可尝试上气道外科手术、也可尝试直接或间接刺激呼吸驱动的药物（如茶碱或乙酰唑胺）、或减少上气道塌陷的药物（如地昔帕明）。《对照研究：腭舌手术治疗中重度阻塞性睡眠呼吸暂停的患者》JAMA，2020年9月 (5)研究的目的是考察了腭舌手术对阻塞性睡眠呼吸暂停综合征（OSA）常规治疗失败患者的疗效。研究纳入常规治疗失败的、症状性的、中重度、阻塞性睡眠呼吸暂停患者101人，随机接受多次腭舌手术（改良悬雍垂腭咽成形术和微创舌体积缩小术）、或常规医疗（例如，改善睡眠姿势或减肥）。89%的患者完成了试验，手术组基线时的平均睡眠呼吸暂停低通气指数为47.9，6个月时为20.8；常规医疗组基线时为45.3，6个月时为34.5（6个月时，组间平均校正后差异为-17.6个事件/小时）。手术组基线时的Epworth嗜睡评分为12.4，6个月时为5.3；常规医疗组基线时为11.1，6个月时为10.5（6个月时，平均基线调整组间差异-6.7）。不良事件：手术组1例术后第5天发生心肌梗死，1例因吐血而住院观察。结论：常规治疗失败的、中重度阻塞性睡眠呼吸暂停症患者，接受悬雍垂腭咽成形术和微创舌体积缩小术，可减少呼吸暂停和低通气事件的发生，改善患者嗜睡症状。肺结核肺结核是结核分枝杆菌感染最常见的部位。（1）原发性肺结核主要发生于儿童期，也可以在青少年或成人中发生，其临床表现在人群中差异很大：低热70%、胸膜炎性胸痛25%、乏力咳嗽咽痛比较少见。X线表现：肺门淋巴结肿大65%，胸腔积液33%，肺部浸润27%。原发性感染后，90%的免疫系统正常者可以控制结核杆菌的进一步复制；随后结核杆菌可能进入潜伏期，10%的感染者进行性的出现肺结核肺炎。（2）复燃性肺结核的患者发热和盗汗更常见，约一半的患者有咳嗽、体重减轻、乏力。X线表现：上叶尖后段受累80-90%，空洞形成20%。《系统回顾和荟萃分析：近距离接触结核病人后，儿童罹患肺结核的风险》Lancet，2020年3月 (6)全球每年有数千万儿童接触结核分枝杆菌，但是，仍没有对受感染儿童罹患结核病的风险的估计，对接触调查和预防治疗的有效性也缺乏了解。在这篇系统回顾和荟萃分析中，纳入了来自34个国家的46个队列研究的数据。评估了137647例结核暴露儿童，对135512例儿童进行了429538人年随访，期间诊断出1299例流行性结核和999例散发性结核。结核感染阳性、但未接受预防治疗的儿童2年累计肺结核发病率明显高于结核感染阴性儿童。其中5岁以下儿童肺结核发病率最高，为19·0%。所有暴露儿童预防治疗的有效性为63%，对于结核感染阳性儿童预防治疗的有效性为91%。结论：结核暴露的婴儿和幼儿罹患结核病的风险非常高，大多数病例发生在接触者调查开始后的几周内。《前瞻性研究：接触耐多药结核病后异烟肼的防治效果》American Journal of Respiratory and Critical Care Medicine，2020年6月 (7)WHO建议单独使用异烟肼或异烟肼与利福平联合使用来治疗潜在的结核病感染。该研究的目的是研究单独使用异烟肼用于预防多药耐药结核感染的有效性。这个前瞻性群组研究纳入4500个肺结核病人和14044个结核暴露家庭，19岁以下的接触者共4216人，只有一半人接受了异烟肼预防治疗。异烟肼的预防作用十分显著，在接触非耐药结核病人时感染风险下降70%，在接触多药耐药结核病人后的感染风险下降81%。在接触异烟肼单药耐药结核病人时，异烟肼的预防作用稍弱（风险比0.80）。在第二项独立研究中，76名接受异烟肼预防的家庭接触者均未感染；而273名未接受异烟肼预防治疗的家庭接触者有8人感染，占3%。结论：即使接触多药耐药结核病患者，异烟肼也能有效降低接触者的结核发病率。《随机对照研究：补充维生素D预防结核杆菌感染》New England Journal of Medicine，2020年7月 (8)研究的目的是评估补充维生素D是否可以预防结核病感染。参与研究的8851名、结核分枝杆菌感染阴性的、维生素D缺乏的儿童，随机分入维生素D组或安慰剂组，干预持续3年。3年后，儿童的维生素D缺乏得到纠正，两组的平均25-羟-维生素D水平分别为31.0ng/mL和10.7ng/mL；但是两组间QuantiFERON-TB试验阳性比例没有差异，分别为3.6%和3.3%（P = 0.42）。维生素D组有21名儿童和安慰剂组有25名儿童被诊断患有结核病，分别有29人和34人因急性呼吸道感染住院治疗，发生率无显著差异。结论：维生素D缺乏的儿童中，补充维生素D没有降低结核感染的风险。肺结核的治疗无HIV感染的、成人的药物敏感性的、肺结核治疗：通常2个月强化治疗以及4-7个月维持治疗。强化阶段通常采用四联药物治疗 [ 包括异烟肼、利福霉素类（利福平、利福喷丁、利福布丁）、吡嗪酰胺、乙胺丁醇 ] ，维持治疗通常采用二联药物治疗（包括异烟肼、利福平）。耐药肺结核包括单药耐药和多药耐药。单药耐药的情况下，可选用其他的一线药物，也可联合氟喹诺酮类。多药耐药的治疗取决于药敏试验，原则是尽可能多的一线药物，再加上一种氟喹诺酮类（左氧氟沙星、莫西沙星）和/或另一种核心二线药物（如贝达喹啉、利奈唑胺）。药物研发进展：普托马尼（pretomanid，硝基咪唑嗪类抗菌药，2019年8月批准上市）。《随机研究：短疗程治疗利福平耐药的肺结核的3期临床研究》New England Journal of Medicine，2019年3月 (9)研究的目的是在对氟喹诺酮类和氨基糖苷类药物敏感的、利福平耐药的、结核患者中开展了一项3期非劣效性试验。共424例患者，随机分别接受含有大剂量莫⻄沙星的短疗程方案（9~11个月）或遵循2011年WHO指南推荐的⻓疗程方案（20个月）。132周后，⻓疗程方案组和短疗程方案中，分别有79.8%和78.8%的参与者报告了良好状态（P=0.02）。两组的严重不良事件发生率分别有45.4%和48.2%。短疗程方案组11.0%参与者和⻓疗程方案组6.4%参与者出现QT间期延⻓，并进行了药物调整。结论：在对氟喹诺酮类药物和氨基糖苷类药物敏感的、利福平耐药的结核患者中，包括大剂量莫西沙星的短疗程方案的主要疗效结局不劣于⻓疗程方案，安全性相似。支气管热成型术支气管热成形术（Bronchial Themoplasty）是一种治疗重度哮喘的手段，经由纤维光学支气管镜导入特质的导管，然后利用该导管对支气管壁施加热能，以削弱支气管平滑肌的收缩力、减轻气道平滑肌的增生。该操作通常需要在中度镇静下进行3次支气管镜下操作，每次间隔3周。主要针对的人群是治疗吸入性糖皮质激素和LABA控制不佳的、重症哮喘患者。但这项操作有风险，对其长期的疗效仍有一定的争议。《TASMA研究：支气管热成型术引起的气道平滑肌减少和对重症哮喘的治疗效果》American Journal of Respiratory and Critical Care Medicine，2020年7月(10)研究的目的是确定支气管热成型术对气道平滑肌的质量的影响，并确定哪一类重症哮喘患者适合接受此项治疗。研究纳入40例重症哮喘患者，随机分为即时支气管热成型术组和延迟支气管热成型术组。即时手术组的中位气道平滑肌质量减少>50%，而延迟组的气管平滑肌的质量无变化（p=0.0004）。即时手术组和延迟手术组中，哮喘控制问卷评分分别降低了0.79和升高了0.09（p=0.006）；哮喘生活质量问卷评分分别升高了0.83和降低了0.02（p=0.04）。治疗反应（n=35）与血清IgE和嗜酸性粒细胞呈正相关，但与气道平滑肌基线质量无关。结论：支气管热成型术后气道平滑肌的质量明显降低。疗效与血清IgE和嗜酸性粒细胞水平相关，而与气道平滑肌的质量无关。《随机对照临床研究：129Xe-MRI引导的一次支气管热成形术》American Journal of Respiratory and Critical Care Medicine，2020年8月 (11)不良事件限制了支气管热成形术在重症哮喘中的应用，该研究的目的是使用氙129磁共振技术（129Xe-MRI）引导下进行支气管热成形术。研究对30例严重哮喘患者进行容积CT和129Xe-MRI，以定量节段性通气缺损，然后被随机分组至磁共振引导组（行一次支气管热成形术治疗6个病变最严重的支气管）、或非引导组（标准的三阶段支气管热成形术）。治疗12周后，磁共振引导组与非引导组相比，生活质量评分改善无显著差异（P = 0.201），但肺通气不良和肺不通气的比例下降更显著（-17.2%；P = 0.009）。磁共振引导组中33%的患者术后哮喘加重；非引导组有73%的患者哮喘加重（P = 0.028）。结论：与标准的三次支气管热成形术相比，磁共振引导下的一次支气管热成形术可以取得类似的短期改善，且围手术期不良事件较少。CT诊断人工智能系统《应用人工智能系统对新型冠状病毒肺炎进行CT诊断、定量和预后评估》 Cell，2020年6月 (12)许多罹患COVID-19的患者发展为肺炎，并迅速发展为呼吸衰竭。然而，快速诊断与鉴别高危患者、并早期干预仍十分具有挑战性。使用大型CT数据库分析4154名患者的资料后，研究人员开发了用以诊断和鉴别诊断新型冠状病毒肺炎的人工智能系统。此人工智能系统能够客观、定量的识别和测量新型冠状病毒肺炎病变CT上的肺部损害指标，如小结节、毛玻璃影、实变影，评价疾病严重程度，也可用于客观、定量的评价药物有效性。结合患者临床指标，如吸氧频率、血氧饱和度、血气分析、肝功能、凝血功能等，可以综合分析并预测患者发展为危重症的可能性和时间。参考文献1.Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. 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New England Journal of Medicine. 2019;380(13):1201-13.9.Huang CC, Becerra MC, Calderon R, Contreras C, Galea J, Grandjean L, et al. Isoniazid Preventive Therapy in Contacts of Multidrug-resistant Tuberculosis. Am J Respir Crit Care Med. 2020.10.Goorsenberg AWM, d'Hooghe JNS, Srikanthan K, Ten Hacken NHT, Weersink EJM, Roelofs J, et al. Bronchial Thermoplasty Induced Airway Smooth Muscle Reduction and Clinical Response in Severe Asthma: The TASMA Randomized Trial. Am J Respir Crit Care Med. 2020.11.Hall CS, Quirk JD, Goss CW, Lew D, Kozlowski J, Thomen RP, et al. Single-Session Bronchial Thermoplasty Guided by (129)Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2020;202(4):524-34.12.Zhang K, Liu X, Shen J, Li Z, Sang Y, Wu X, et al. Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography. Cell. 2020;181(6):1423-33 e11.

呼吸科星期二 2020年11月3日 第2集FDA 免疫检查点抑制剂进入肺癌的一线治疗NEJM 治疗耐药结核时，短疗程方案不劣于长疗程方案Cell CT的人工智能系统可用于诊断COVID-19德瓦鲁单抗（durvalumab）德瓦鲁单抗是一种PD-L1单抗，此前已被批准用于治疗晚期膀胱癌和无法切除的3期非小细胞肺癌。2020年3月，德瓦鲁单抗被批准用于广泛期小细胞肺癌联合标准化疗的一线用药。《CASPIAN研究：德瓦鲁单抗联合铂-依托泊苷治疗广泛期小细胞肺癌的疗效》Lancet，2019年11月 (1)这项研究的目的是评估德瓦鲁单抗与依托泊苷联合顺铂或卡铂治疗广泛期小细胞肺癌的疗效，对照组方案是依托泊苷联合顺铂或卡铂。这项随机、开放标签、三期试验，纳入未经治疗的、广泛期小细胞肺癌患者537人，随机分为德瓦鲁单抗+铂/依托泊苷组、铂/依托泊苷组。联合德瓦鲁单抗组总生存率显著改善，优势比为0·73（p = 0·0047）。联合德瓦鲁单抗组和不使用德瓦鲁单抗组中，中位总生存期分别为13·0个月和10·3个月；随访至18个月时，两组分别有34%和25%的患者存活。结论：一线德瓦鲁单抗联合铂/依托泊苷显著改善广泛期小细胞肺癌患者的总生存率。纳武利尤单抗+ 伊匹木单抗（nivolumab+ipilimumab）2020年5月，FDA批准纳武利尤单抗（抗PD-1单抗）和伊匹木单抗（CTLA-4单抗），两个药物联合低剂量化疗作为转移或复发的非小细胞肺癌的一线治疗方案。《CheckMate 227研究：纳武利尤单抗联合伊匹木单抗治疗晚期非小细胞肺癌的3期临床研究》New England of Medicine，2019年11月 (2)此项开放标签的3期临床研究的目的是，评价晚期非小细胞肺癌患者中使用PD-1单抗（纳武利尤单抗）+CTLA-4单抗（伊匹木单抗）联合治疗的长期获益。研究纳入PD-L1表达水平≥1%的、Ⅳ期或复发的、非小细胞肺癌患者，随机分入纳武利尤单抗+伊匹木单抗双联治疗组、或纳武利尤单抗单药治疗、或化疗组；同时也纳入了PD-L1表达水平＜1%的患者，随机分三组中。所有患者之前均未接受过化疗。在PD-L1表达水平≥1%的患者中，纳武利尤单抗+伊匹木单抗组和化疗组的中位总生存期分别为17.1个月和14.9个月（P=0.007），2年总生存率分别为40.0%和32.8%，中位缓解时间分别为23.2个月和6.2个月。在PD-L1表达水平＜1%的患者中也观察到了总生存期获益，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.2个月和12.2个月。全部患者中，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.1个月和13.9个月，严重不良事件发病率分别为32.8%和36.0%。结论：在非小细胞肺癌患者中，纳武利尤单抗+伊匹木单抗一线治疗组的总生存期超过化疗组，且与PD-L1表达水平无关。长期随访中未发现新的安全性问题。阻塞性睡眠呼吸暂停阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）是一种因睡眠过程中上气道反复塌陷引起的、以阻塞性呼吸暂停和低通气为特征的疾病。对于存在白天睡眠过多、打鼾和睡眠中窒息或倒吸气等症状的、高龄、肥胖、男性患者，应该考虑这个诊断。多导睡眠监测图是诊断的金标准，诊断标准为：无相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥15次/小时；伴有相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥5次/小时。相关症状包括：嗜睡、疲劳、失眠，觉醒时存在憋气、倒吸气或窒息，或者观察者发现患者习惯性打鼾、呼吸中断。相关疾病包括：高血压、心境障碍、认知功能障碍、冠心病、脑卒中、心力衰竭、心房颤动或2型糖尿病。《前瞻性研究：睡眠呼吸障碍和失眠与高血压和糖尿病的关系》American Journal of Respiratory and Critical Care Medicine，2020年7月 (3)这项前瞻性研究，通过长达6年的随访，旨在调查美国西班牙裔/拉丁裔人群中，睡眠呼吸障碍和失眠与高血压和糖尿病发生之间的关联，共纳入11623名参与者，女性占52.6％，平均年龄41.1±14.9岁。存在睡眠呼吸障碍的人群，与没有睡眠呼吸障碍的人群比较，高血压发生的风险比1.54，糖尿病发生风险比1.37。失眠与高血压有关（风险比1.37），其中男性关联性更强。结论：睡眠呼吸障碍与高血压和糖尿病有关。失眠与高血压有关。这些结果支持将睡眠障碍作为预防和减少高血压、糖尿病的靶标。《SAVE研究：持续气道正压治疗对同时患有OSA和稳定性冠心病的患者的糖尿病的影响》Diabetes Care，2020年7月 (4)研究试图确定在同时患有稳定性冠心病和OSA患者中，长期持续气道正压（CPAP）通气治疗对血糖控制和糖尿病风险的影响。研究收集了888名同时患有稳定性冠心病和OSA患者，一组接受CPAP加常规治疗，另一组接受常规治疗，中位随访时间为4.3年。糖尿病的患者中，不同治疗组的血糖、糖化血红蛋白或降糖药物使用方面无显著差异。糖尿病前期、或新诊断的糖尿病患者中，组间也没有显著差异。有趣的是，女性糖尿病患者在常规治疗组表现较差，而接受CPAP治疗后病情更稳定。结论：在同时患有稳定性冠心病和OSA患者中，尚无证据证明长期CPAP治疗对血糖控制有益。但研究中发现的性别差异仍需进一步验证。阻塞性睡眠呼吸暂停的治疗一般治疗包括：减重、运动、侧卧位睡眠、避免酒精、避免使用精神类药物。主要治疗方法是气道正压治疗，常见模式包括持续气道正压（CPAP）、双水平气道正压（BPAP）和自动调定式的气道正压（APAP），最常用的是CPAP。替代治疗方法包括：轻中度患者可尝试口腔矫正器、存在上气道阻塞的患者可尝试上气道外科手术、也可尝试直接或间接刺激呼吸驱动的药物（如茶碱或乙酰唑胺）、或减少上气道塌陷的药物（如地昔帕明）。《对照研究：腭舌手术治疗中重度阻塞性睡眠呼吸暂停的患者》JAMA，2020年9月 (5)研究的目的是考察了腭舌手术对阻塞性睡眠呼吸暂停综合征（OSA）常规治疗失败患者的疗效。研究纳入常规治疗失败的、症状性的、中重度、阻塞性睡眠呼吸暂停患者101人，随机接受多次腭舌手术（改良悬雍垂腭咽成形术和微创舌体积缩小术）、或常规医疗（例如，改善睡眠姿势或减肥）。89%的患者完成了试验，手术组基线时的平均睡眠呼吸暂停低通气指数为47.9，6个月时为20.8；常规医疗组基线时为45.3，6个月时为34.5（6个月时，组间平均校正后差异为-17.6个事件/小时）。手术组基线时的Epworth嗜睡评分为12.4，6个月时为5.3；常规医疗组基线时为11.1，6个月时为10.5（6个月时，平均基线调整组间差异-6.7）。不良事件：手术组1例术后第5天发生心肌梗死，1例因吐血而住院观察。结论：常规治疗失败的、中重度阻塞性睡眠呼吸暂停症患者，接受悬雍垂腭咽成形术和微创舌体积缩小术，可减少呼吸暂停和低通气事件的发生，改善患者嗜睡症状。肺结核肺结核是结核分枝杆菌感染最常见的部位。（1）原发性肺结核主要发生于儿童期，也可以在青少年或成人中发生，其临床表现在人群中差异很大：低热70%、胸膜炎性胸痛25%、乏力咳嗽咽痛比较少见。X线表现：肺门淋巴结肿大65%，胸腔积液33%，肺部浸润27%。原发性感染后，90%的免疫系统正常者可以控制结核杆菌的进一步复制；随后结核杆菌可能进入潜伏期，10%的感染者进行性的出现肺结核肺炎。（2）复燃性肺结核的患者发热和盗汗更常见，约一半的患者有咳嗽、体重减轻、乏力。X线表现：上叶尖后段受累80-90%，空洞形成20%。《系统回顾和荟萃分析：近距离接触结核病人后，儿童罹患肺结核的风险》Lancet，2020年3月 (6)全球每年有数千万儿童接触结核分枝杆菌，但是，仍没有对受感染儿童罹患结核病的风险的估计，对接触调查和预防治疗的有效性也缺乏了解。在这篇系统回顾和荟萃分析中，纳入了来自34个国家的46个队列研究的数据。评估了137647例结核暴露儿童，对135512例儿童进行了429538人年随访，期间诊断出1299例流行性结核和999例散发性结核。结核感染阳性、但未接受预防治疗的儿童2年累计肺结核发病率明显高于结核感染阴性儿童。其中5岁以下儿童肺结核发病率最高，为19·0%。所有暴露儿童预防治疗的有效性为63%，对于结核感染阳性儿童预防治疗的有效性为91%。结论：结核暴露的婴儿和幼儿罹患结核病的风险非常高，大多数病例发生在接触者调查开始后的几周内。《前瞻性研究：接触耐多药结核病后异烟肼的防治效果》American Journal of Respiratory and Critical Care Medicine，2020年6月 (7)WHO建议单独使用异烟肼或异烟肼与利福平联合使用来治疗潜在的结核病感染。该研究的目的是研究单独使用异烟肼用于预防多药耐药结核感染的有效性。这个前瞻性群组研究纳入4500个肺结核病人和14044个结核暴露家庭，19岁以下的接触者共4216人，只有一半人接受了异烟肼预防治疗。异烟肼的预防作用十分显著，在接触非耐药结核病人时感染风险下降70%，在接触多药耐药结核病人后的感染风险下降81%。在接触异烟肼单药耐药结核病人时，异烟肼的预防作用稍弱（风险比0.80）。在第二项独立研究中，76名接受异烟肼预防的家庭接触者均未感染；而273名未接受异烟肼预防治疗的家庭接触者有8人感染，占3%。结论：即使接触多药耐药结核病患者，异烟肼也能有效降低接触者的结核发病率。《随机对照研究：补充维生素D预防结核杆菌感染》New England Journal of Medicine，2020年7月 (8)研究的目的是评估补充维生素D是否可以预防结核病感染。参与研究的8851名、结核分枝杆菌感染阴性的、维生素D缺乏的儿童，随机分入维生素D组或安慰剂组，干预持续3年。3年后，儿童的维生素D缺乏得到纠正，两组的平均25-羟-维生素D水平分别为31.0ng/mL和10.7ng/mL；但是两组间QuantiFERON-TB试验阳性比例没有差异，分别为3.6%和3.3%（P = 0.42）。维生素D组有21名儿童和安慰剂组有25名儿童被诊断患有结核病，分别有29人和34人因急性呼吸道感染住院治疗，发生率无显著差异。结论：维生素D缺乏的儿童中，补充维生素D没有降低结核感染的风险。肺结核的治疗无HIV感染的、成人的药物敏感性的、肺结核治疗：通常2个月强化治疗以及4-7个月维持治疗。强化阶段通常采用四联药物治疗 [ 包括异烟肼、利福霉素类（利福平、利福喷丁、利福布丁）、吡嗪酰胺、乙胺丁醇 ] ，维持治疗通常采用二联药物治疗（包括异烟肼、利福平）。耐药肺结核包括单药耐药和多药耐药。单药耐药的情况下，可选用其他的一线药物，也可联合氟喹诺酮类。多药耐药的治疗取决于药敏试验，原则是尽可能多的一线药物，再加上一种氟喹诺酮类（左氧氟沙星、莫西沙星）和/或另一种核心二线药物（如贝达喹啉、利奈唑胺）。药物研发进展：普托马尼（pretomanid，硝基咪唑嗪类抗菌药，2019年8月批准上市）。《随机研究：短疗程治疗利福平耐药的肺结核的3期临床研究》New England Journal of Medicine，2019年3月 (9)研究的目的是在对氟喹诺酮类和氨基糖苷类药物敏感的、利福平耐药的、结核患者中开展了一项3期非劣效性试验。共424例患者，随机分别接受含有大剂量莫⻄沙星的短疗程方案（9~11个月）或遵循2011年WHO指南推荐的⻓疗程方案（20个月）。132周后，⻓疗程方案组和短疗程方案中，分别有79.8%和78.8%的参与者报告了良好状态（P=0.02）。两组的严重不良事件发生率分别有45.4%和48.2%。短疗程方案组11.0%参与者和⻓疗程方案组6.4%参与者出现QT间期延⻓，并进行了药物调整。结论：在对氟喹诺酮类药物和氨基糖苷类药物敏感的、利福平耐药的结核患者中，包括大剂量莫西沙星的短疗程方案的主要疗效结局不劣于⻓疗程方案，安全性相似。支气管热成型术支气管热成形术（Bronchial Themoplasty）是一种治疗重度哮喘的手段，经由纤维光学支气管镜导入特质的导管，然后利用该导管对支气管壁施加热能，以削弱支气管平滑肌的收缩力、减轻气道平滑肌的增生。该操作通常需要在中度镇静下进行3次支气管镜下操作，每次间隔3周。主要针对的人群是治疗吸入性糖皮质激素和LABA控制不佳的、重症哮喘患者。但这项操作有风险，对其长期的疗效仍有一定的争议。《TASMA研究：支气管热成型术引起的气道平滑肌减少和对重症哮喘的治疗效果》American Journal of Respiratory and Critical Care Medicine，2020年7月(10)研究的目的是确定支气管热成型术对气道平滑肌的质量的影响，并确定哪一类重症哮喘患者适合接受此项治疗。研究纳入40例重症哮喘患者，随机分为即时支气管热成型术组和延迟支气管热成型术组。即时手术组的中位气道平滑肌质量减少>50%，而延迟组的气管平滑肌的质量无变化（p=0.0004）。即时手术组和延迟手术组中，哮喘控制问卷评分分别降低了0.79和升高了0.09（p=0.006）；哮喘生活质量问卷评分分别升高了0.83和降低了0.02（p=0.04）。治疗反应（n=35）与血清IgE和嗜酸性粒细胞呈正相关，但与气道平滑肌基线质量无关。结论：支气管热成型术后气道平滑肌的质量明显降低。疗效与血清IgE和嗜酸性粒细胞水平相关，而与气道平滑肌的质量无关。《随机对照临床研究：129Xe-MRI引导的一次支气管热成形术》American Journal of Respiratory and Critical Care Medicine，2020年8月 (11)不良事件限制了支气管热成形术在重症哮喘中的应用，该研究的目的是使用氙129磁共振技术（129Xe-MRI）引导下进行支气管热成形术。研究对30例严重哮喘患者进行容积CT和129Xe-MRI，以定量节段性通气缺损，然后被随机分组至磁共振引导组（行一次支气管热成形术治疗6个病变最严重的支气管）、或非引导组（标准的三阶段支气管热成形术）。治疗12周后，磁共振引导组与非引导组相比，生活质量评分改善无显著差异（P = 0.201），但肺通气不良和肺不通气的比例下降更显著（-17.2%；P = 0.009）。磁共振引导组中33%的患者术后哮喘加重；非引导组有73%的患者哮喘加重（P = 0.028）。结论：与标准的三次支气管热成形术相比，磁共振引导下的一次支气管热成形术可以取得类似的短期改善，且围手术期不良事件较少。CT诊断人工智能系统《应用人工智能系统对新型冠状病毒肺炎进行CT诊断、定量和预后评估》 Cell，2020年6月 (12)许多罹患COVID-19的患者发展为肺炎，并迅速发展为呼吸衰竭。然而，快速诊断与鉴别高危患者、并早期干预仍十分具有挑战性。使用大型CT数据库分析4154名患者的资料后，研究人员开发了用以诊断和鉴别诊断新型冠状病毒肺炎的人工智能系统。此人工智能系统能够客观、定量的识别和测量新型冠状病毒肺炎病变CT上的肺部损害指标，如小结节、毛玻璃影、实变影，评价疾病严重程度，也可用于客观、定量的评价药物有效性。结合患者临床指标，如吸氧频率、血氧饱和度、血气分析、肝功能、凝血功能等，可以综合分析并预测患者发展为危重症的可能性和时间。参考文献1.Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-39.2.Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim S-W, Carcereny Costa E, et al. Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2019;381(21):2020-31.3.Li X, Sotres-Alvarez D, Gallo LC, Ramos AR, Aviles-Santa L, Perreira KM, et al. Associations of Sleep Disordered Breathing and Insomnia with Incident Hypertension and Diabetes: The Hispanic Community Health Study/Study of Latinos. Am J Respir Crit Care Med. 2020.4.Loffler KA, Heeley E, Freed R, Meng R, Bittencourt LR, Gonzaga Carvalho CC, et al. Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease. Diabetes Care. 2020;43(8):1859-67.5.MacKay S, Carney AS, Catcheside PG, Chai-Coetzer CL, Chia M, Cistulli PA, et al. Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial. JAMA. 2020.6.Martinez L, Cords O, Horsburgh CR, Andrews JR. The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis. Lancet. 2020;395(10228):973-84.7.Ganmaa D, Uyanga B, Zhou X, Gantsetseg G, Delgerekh B, Enkhmaa D, et al. Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease. N Engl J Med. 2020;383(4):359-68.8.Nunn AJ, Phillips PPJ, Meredith SK, Chiang C-Y, Conradie F, Dalai D, et al. A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis. New England Journal of Medicine. 2019;380(13):1201-13.9.Huang CC, Becerra MC, Calderon R, Contreras C, Galea J, Grandjean L, et al. Isoniazid Preventive Therapy in Contacts of Multidrug-resistant Tuberculosis. Am J Respir Crit Care Med. 2020.10.Goorsenberg AWM, d'Hooghe JNS, Srikanthan K, Ten Hacken NHT, Weersink EJM, Roelofs J, et al. Bronchial Thermoplasty Induced Airway Smooth Muscle Reduction and Clinical Response in Severe Asthma: The TASMA Randomized Trial. Am J Respir Crit Care Med. 2020.11.Hall CS, Quirk JD, Goss CW, Lew D, Kozlowski J, Thomen RP, et al. Single-Session Bronchial Thermoplasty Guided by (129)Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2020;202(4):524-34.12.Zhang K, Liu X, Shen J, Li Z, Sang Y, Wu X, et al. Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography. Cell. 2020;181(6):1423-33 e11.

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

In this episode, an expert medical oncology panel led by Elizabeth R. Plimack, MD, MS, with Brian A. Costello, MD, and Martin H. Voss, MD, discusses clinical pearls for the management of patients with metastatic renal cell carcinoma (RCC). Topics include:Treating beyond progression with immunotherapyManagement of patients with less common histologic subtypes of RCCPotential biomarkers for RCCAdverse event managementPresenters:Elizabeth R. Plimack, MD, MSChief, Division of Genitourinary Medical Oncology Director, Genitourinary Clinical Research Professor, Department of Hematology/Oncology Fox Chase Cancer Center Temple Health Philadelphia, PennsylvaniaBrian A. Costello, MDAssociate Professor of Oncology and UrologyDivision of Medical OncologyMayo ClinicRochester, MinnesotaMartin H. Voss, MDClinical Director, Genitourinary Medical Oncology ServiceMemorial Sloan Kettering Cancer CenterAssistant Professor Weill Cornell Medical CollegeNew York, New YorkContent based on an online CME program supported by educational grants from Eisai, Exelixis, and Pfizer and EMD Serono.Link to full program:https://bit.ly/32IS9gx

In this episode, an expert medical oncology panel, led by Elizabeth R. Plimack, MD, with Brian A. Costello, MD, and Martin H. Voss, MD, discusses current best practices for the second-line treatment and beyond of patients with metastatic renal cell carcinoma (RCC). Topics include:•           Treatment sequencing with IO and TKI therapies•           Optimizing dose for patients with preexisting toxicities•           Considerations for local control of metastatic sites •           Ongoing clinical trials Presenters:Elizabeth R. Plimack, MD, MSChief, Division of Genitourinary Medical Oncology Director, Genitourinary Clinical Research Professor, Department of Hematology/Oncology Fox Chase Cancer Center Temple Health Philadelphia, PennsylvaniaBrian A. Costello, MDAssociate Professor of Oncology and UrologyDivision of Medical OncologyMayo ClinicRochester, MinnesotaMartin H. Voss, MDClinical Director, Genitourinary Medical Oncology ServiceMemorial Sloan Kettering Cancer CenterAssistant Professor Weill Cornell Medical CollegeNew York, New YorkContent based on an online CME program supported by an educational grant from Eisai, Exelixis, and Pfizer and EMD Serono.Link to full program:https://bit.ly/32IS9gx

This week, we'll be talking about an extended follow-up of a phase III trial that investigated first-line nivolumab and ipilimumab vs sunitinib in advanced renal cell carcinoma. Then we'll go over a research letter that identified strong predictors of response to immune checkpoint inhibitor treatment. Lastly, we'll review a report on e-cigarette secondhand smoke exposure experienced by middle and high school students.Coverage of stories discussed this week on ascopost.com:Extended Follow-up of CheckMate 214: Nivolumab/Ipilimumab vs Sunitinib as First-Line Treatment for Advanced RCCKey Predictors of Response Rates to PD-1/PD-L1 Inhibitor Therapy Across Cancer TypesExposure to Secondhand E-Cigarette Aerosols Increasing Among Middle and High School Students