Podcasts about ccrcc

The Clark County Republican Central Committee has adopted a resolution condemning political violence, following assassination attempts on former President Donald Trump. Read the full story at https://www.clarkcountytoday.com/news/ccrcc-adopts-resolution-condemning-political-violence/ on www.ClarkCountyToday.com. Hashtags: #politicalviolence #TrumpAssassination #JimWalsh #MattBumala #CCRP #ClarkCountyWa #localnews

Visit learnAMAstyle.com to uplevel your writing and editing skills with free downloads on medical writing and editing. The FDA has approved vonoprazan (Voquenza) for treating non-erosive gastroesophageal reflux disease (GERD) in adults. Vonoprazan is an oral potassium-competitive acid blocker (PCAB) already approved for erosive esophagitis and Helicobacter pylori infection. PCABs are a new class of medicines that inhibit stomach acid secretion. Non-erosive GERD is the most common form of GERD, affecting around 45 million US adults, with about 15 million treated with prescription medication annually. Many patients remain dissatisfied with existing treatments, experiencing symptoms that affect their quality of life. The approval of vonoprazan was based on the Phalcon-Nerd-301 study, a Phase 3 trial showing it significantly reduced heartburn episodes and provided more heartburn-free days and nights compared to placebo. The trial included 772 adults with frequent heartburn, demonstrating vonoprazan's effectiveness over placebo. The FDA has granted fast track designation to ADI-270 for metastatic or advanced clear cell renal cell carcinoma (ccRCC) in patients who previously received an immune checkpoint inhibitor and a VEGF inhibitor. ADI-270 is a CD70-targeted gamma delta CAR T-cell therapy designed to enhance resilience to the tumor microenvironment. A phase 1/2 trial will evaluate ADI-270 in patients with confirmed ccRCC who have been previously treated. The primary endpoints are the incidence of dose-limiting toxicities and the proportion of treatment-emergent adverse effects. The FDA has granted Fast Track and Regenerative Medicine Advanced Therapeutic (RMAT) designations to Lomecel-B, an investigational MSC therapy for Alzheimer's disease (AD). Lomecel-B aims to address neurodegeneration in AD and showed positive results in the CLEAR MIND Phase 2a trial. Visit learnAMAstyle.com to uplevel your writing and editing skills with free downloads on medical writing and editing.

In this podcast, UROONCO RCC chief editor Dr. Carmen Mir (ES) interviews Prof. Michael Hofman from the Peter MacCallum Cancer Centre, Australia, on the results of his study “First-in-human safety, imaging and dosimetry of [68Ga]Ga-DPI-4452, a novel CA IX-targeting peptide, in patients with clear cell renal cell carcinoma (ccRCC)”. Prof. Hofman discusses the data he presented at ASCO GU24 in San Francisco and suggests that these first-in-human findings with radiolabelled DPI-4452 are encouraging for the subsequent evaluation of treatment with [177Lu]Lu-DPI-4452.[68Ga]Ga-DPI-4452 provides exceptional images in patients with ccRCC without clinically significant toxicity. Very high SUVs and tumour-to-background ratios suggest potential for use in both diagnostics and patient selection for therapy. The tumour retention and rapid elimination support potential of [177Lu]Lu-DPI-4452 radioligand therapy. For more details on this study, you can read the abstract on the UROONCO Kidney Cancer educational platform.

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. 

Dr. Eric Singer highlights the recent rapid recommendation update from ASCO on the management of metastatic renal cell cancer (ccRCC), based on the review of evidence from the phase III COSMIC 313 trial. Dr. Singer reviews the discussion from the Expert Panel and emphasizes clinicians should continue to follow the previously issued recommendations for the management of metastatic ccRCC. He also mentions future directions, ongoing clinical trials, and outstanding questions for these evidence-based guidelines. Read the latest update, “Management of Metastatic Renal Clear Cell Cancer: ASCO Guideline Rapid Recommendation Update” at www.asco.org/genitourinary-cancer-guidelines.  

The Meeting

Gotta get this out a couple of days early. CCRCC tonight!

BUFFALO, NY- September 20, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on September 15, 2023, entitled, “Potential repurposing of DPP4 inhibitors for target therapy resistance in renal cell carcinoma.” In their new editorial, researchers Kuniko Horie and Satoshi Inoue from Saitama Medical University and Tokyo Metropolitan Institute for Geriatrics and Gerontology discuss renal cell carcinoma (RCC) — a major adult kidney cancer, which is often incidentally discovered as an asymptomatic disease on imaging in the developed countries. RCC has the most fatal disease among urological cancers, as a recent 5-year relative survival rate in the U.S. (2009–2015) is less than 80%. While RCC is known as a cancer resistant to chemo- and radio-therapies, the prognosis of RCC has been remarkably improved after the clinical application of tyrosine kinase inhibitors (TKIs) and immunotherapy. The rationale for the efficacy of TKIs in RCC is mainly based on the angiogenetic status, particularly in clear cell RCC (ccRCC) that is the most common type of RCC (70–75% of RCC), in which the loss of function mutation of Von Hippel-Lindau (VHL) tumor suppressor gene activates hypoxia inducible factor (HIF) and vascular endothelial growth factor (VEGF) pathways. The first-line TKIs that predominantly target VEGF receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) (e.g., sunitinib and sorafenib) have been clinically used since late 2000s, and the second-line TKIs such as cabozantinib, which targets more receptor tyrosine kinases including MET and TAM kinases as well as VEGFR, have been further applied to the treatment of advanced RCC since early 2010s in which the first-line TKIs are ineffective. “In our recent study, we established a panel of patient-derived ccRCC spheroid cultures with the enhancement of cancer stemness gene signature including DPP4 [9]. Focusing on TKI sunitinib sensitivity, we demonstrated that DPP4 inhibition increased sunitinib efficacy in DPP4-high RCC spheroids and DPP4 was upregulated in sunitinib-resistant RCC cells.” DOI - https://doi.org/10.18632/oncotarget.28463 Correspondence to - Satoshi Inoue - sinoue07@gmail.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28463 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, renal cell carcinoma (RCC), tyrosine kinase inhibitor (TKI), Dipeptidyl peptidase IV (DPP4), drug resistance, drug repurposing About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

What happened?

Drs. Pedro Barata and Naomi Haas discuss the emergence of clinical trials investigating triplet combinations in advanced renal cell carcinoma, factors that influence treatment decisions, strategies to personalize therapies in the frontline setting, including response-adaptive treatment strategies, and the use of biomarkers such as gene expression analysis to guide initial therapy. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata. I'm your guest host of the ASCO Daily News Podcast today. I'm an associate professor of medicine and also a GU medical oncologist at University Hospital Seidman Cancer Center, Case Western University in Cleveland, Ohio. I'm also an associate editor for the ASCO Educational Book. Today I'm really delighted to welcome Dr. Naomi Haas, the director of the Prostate and Kidney Cancer Program at the Abramson Cancer Center and professor of medicine at the University of Pennsylvania.  Welcome, Dr. Haas. Dr. Naomi Haas: Thank you, Dr. Barata. It's a pleasure to be interviewed. Dr. Pedro Barata: Thank you. As you know, we've seen significant strides in the frontline treatment for patients with advanced clear cell renal cell carcinoma (RCC), and there are multiple doublet regimens that are now the standard of care for those patients. The goal for us to chat today is to discuss the emergence of clinical trials that are really investigating triple combinations and the factors that influence treatment decisions around triplet combinations for patients with advanced renal cell carcinoma. I want to congratulate you for the great work that you did in a recently published article in the 2023 ASCO Educational Book. So thank you for your contributions. And just before we get started, I just want to highlight that our full disclosures are available in the transcript of this episode. So, Dr. Haas, again, it's great to have you. Thank you for taking the time. Let me get started. So, we know that there are multiple standard of care doublet regimens, all of them immunotherapy-based combos, and they usually include 1 checkpoint inhibitor or 2, such as ipilimumab plus nivolumab or a combination of an immune checkpoint inhibitor with a VEGF TKI. And we have a number of examples like that. Can you tell us about the trials that have emerged exploring triplet therapies in the first-line setting for patients with advanced RCC? Dr. Naomi Haas: Sure, and I'm going to focus just on triplet therapies that are just about ready to go. But as you know, Pedro, there are probably many different combinations that we'll see in the future. Some of the combinations that have already been conducted as clinical trials include combinations of VEGF receptor tyrosine kinase inhibitors along with immune checkpoint inhibitors. I'll highlight one which was batiraxcept plus cabozantinib and nivolumab, and it's a combination of VEGF inhibitor, immune checkpoint inhibitor, and also an AXL inhibitor. So, most of these capitalize on other vulnerabilities with renal cell carcinoma.  So, as you said, they build on the tyrosine kinase inhibitor pathway or on the immune checkpoint inhibitor pathway. Some of them are combining drugs such as CDK inhibitors. There was axitinib plus nivolumab plus palbociclib trial that is getting ready to launch. Others are combining the use of belzutifan, which is a HIF inhibitor in combination with VEGF inhibitor and immune checkpoint inhibitor. There are a couple of those that are ongoing, one of them looking at combinations with lenvatinib. And I think there are also trials getting ready to launch that are using it in combination with cabozantinib and nivolumab.  Additionally, another very interesting direction is trying to affect the gut microbiome. And there was a clinical trial presented by Dr. Monty Pal at the gut microbiome session at ASCO, which combined CBM-588, which is a probiotic, in combination with cabozantinib and nivolumab. And that showed an improvement in progression-free survival compared to the combination of cabozantinib and nivolumab alone. And previously there was work published using CBM-588 in combination with ipilimumab and nivolumab. So that's an area of high interest to patients. But most of these combinations capitalize on either vulnerabilities, signs of resistance in pathways or in adding other pathways that have previously been unaddressed in renal cell carcinoma, and are combined with pathways that we know are effective. Dr. Pedro Barata: Wow, that's a fantastic overview of some of the approaches being considered in the frontline, so thank you for that. And actually to your point, some of them we've seen some data, others more later stages of development. So with that in mind, we also know that we have on one side of the story we have how much of these combos of triplets can actually be effective and help patients. From the other perspective is about tolerability, treatment options, and patient health. They're both very important considerations.  Can you tell us a little bit about the safety profile of these triplet combos? I know we're talking about many different things. The microbiome triplet has a different safety profile than perhaps a combination with a TKI and different checkpoints, for instance. Can you tell us a little bit about what we expect from the safety profile when we start to combine these therapies in the upfront setting?  Dr. Naomi Haas: Sure. I think 2 of the very tolerable triplet regimens have been the combination of the CBM-588 in combination with ipilimumab and nivolumab. Really in those combinations, the authors at least have demonstrated that there has not been a great difference between the two study arms of either the doublet or the doublet in combination with the CBM-588 trial. And that's based on basically changing the bacterial flora of the gut. The Avera trial, which was using the AXL inhibitor in combination with cabozantinib and nivolumab, also seems to have a very tolerable safety profile. Now, this trial was not compared to sort of a standard of care arm, so it's a little bit difficult. A standard of care arm that I would have considered for this clinical trial would have been to use either cabozantinib alone or cabozantinib with nivolumab. Instead, this was more of a dose-finding protocol. So, more work needs to be done with that, but the side effects of that combination additive to what we already know seem to be just infusion reactions from the AXL inhibitor.  The trial that got the most attention so far has been COSMIC-313, which was combining cabozantinib with ipilimumab and nivolumab upfront. And of course, the concern with this triplet combination was that there was more hepatotoxicity seen and it was difficult to know whether the hepatotoxicity was from the combinations of the immune checkpoint inhibitors or the use of the cabozantinib. And although the trial showed an improvement in progression-free survival, it did not show as many complete responses as the comparator arm. And the other concern was that there was quite a bit of dropout due to toxicity. And of course, we don't have the overall survival endpoint for that trial yet. Dr. Pedro Barata: Great, thank you for that. I agree completely. We've seen many different safety profiles with these different triplets.  Let me touch base on a slightly different topic, and that has to do with what kind of strategies can we think to personalize treatment for clear cell RCC in the frontline. And this is not necessarily applicable only to triplet therapy. There are also some efforts with doublets, but the goal is, I would argue, is response adaptive treatment strategies or even the use of upfront biomarkers such as gene expression analysis, for example, to help us guide initial therapy. Can you give us an idea what your thoughts are about what is coming? What do you think the future will look like in terms of developing this like a biomarker-based approach? What kind of factors or markers we can use to select who gets what in the frontline setting? Dr. Naomi Haas: Sure. So, I'll just highlight ahead of that that one important biomarker that we're already using is the IMDC criteria, which I think if that algorithm had not been developed, we would be struggling a lot in renal cancer and that's, of course, the algorithm that uses the thing such as performance status, hemoglobin, calcium, and time for the development of metastatic disease as well as the neutrophil count and the platelet count. And that has helped us divide categories of patients with clear cell renal cell carcinoma into poor risk, intermediate risk, or favorable risk categories. And that was recently validated in the immune therapy combinations that were previously been validated just in VEGF inhibitor therapies.  But the other useful, let's start with clinical tools that I think are going to be very important are the health-related quality of life tools which primarily measure things such as functional health, as well as toxicity. And one of these is the FKSI-19 score which captures most renal disease-related symptoms, treatments, side effects, and functional well-being. And this has been implemented in some trials and are looked at over time whether the patient's functional status improves. And patients who are responding to therapies generally will improve as far as their overall well-being. Although that can be difficult as a tool because if patients are experiencing toxicity, those signs might not be apparent. But that's one tool that's being used.  Now, people, both patient advocates and patients, have pointed out that it's very hard to use a tool like this in real life to implement in clinic, but there are efforts being carried out to make these tools a little bit easier so that people can use them day-to-day. So, I can see that being implemented more often.  The others have to do with response assessments, and I think it's very important to look at immune-related responses which kind of builds on the resist response, but it uses two dimensions of measurement as opposed to one dimension of measurement. And looking at those, we know now that patients who have what we call a deep response, so something better than a 75% shrinkage or even a 90% shrinkage in a very short period of time tend to be those patients who behave like patients who have complete responses. And both progression-free survival and overall survivals seem to be going in a very encouraging way looking at these tools so you could see that this tool could be implemented in real life with treating a patient and if they have a very deep response quickly, you can feel, the physician or the APP, could be very confident that the patient is going to do well for a long period of time. I think the tools that we're waiting for the most, however, are as you said, the biomarker tools. And this is where we still have a lot of work to do, but one example of this is the transcriptomics which has been conducted in both the atezolizumab-based trials such as the IMmotion trials, and also to some extent with the JAVELIN trials, the avelumab and axitinib trials. And this goes back to looking at the tissues sample and looking at transcriptomics which show mRNA expression as well as some alterations in some of the important genes such as BAP1 and PRBM1.  And those tools have been implemented, especially in the IMmotion trial, there were 7 clusters identified, and two of the clusters are groups of patients whose tumors have transcriptomics that indicate that they would respond well to a VEGF inhibitor. And a couple of them also showed very good responses to immune checkpoint pathways. There were additional pathways which suggested that patients wouldn't be responsive to either of these. And there is a trial called OPTIC that is funded by the Department of Defense (DOD) which is currently applying these transcriptomics, and then assigning patients to get either a VEGF IO therapy combination or a dual immune checkpoint inhibitor combination, based on their transcriptomics.  And I think what everybody would really like to see is, number 1, that these transcriptomics consistently bear out that there isn't irregularity in using these as predictors. So, they do need to be validated. But I think if there was a quick and easy way to do this, to assign patients to therapies based on these profiles, that would perhaps go a long way in predicting what therapy a patient should start with.  Another useful tool is the development of artificial intelligence. And there are a number of companies that are looking at these tools. We're implementing this retrospectively in the ASSURE trial, which was the adjuvant seraphinib synontib or placebo trial, for patients at high risk for RCC. And we're working with a company to identify, using AI, looking at the slides. And I think that if these kinds of techniques, which are already being used in prostate cancer, are something that can be developed, then what I could see in the future is that a patient's slide could be tested very quickly, and that that might also indicate things that perhaps we can't see under the microscope, as far as either a response to treatment or a risk. So, you could use that in the adjuvant setting to predict whether a patient might need adjuvant therapy or not. So I can see those being implemented.  And then the third is looking at cell-free DNA. And there are many different mechanisms that have been tested in other solid tumors, using either circulating tumor DNA or cell-free DNA. Now, the circulating tumor DNA seems to be a little bit more difficult to assess in metastatic kidney cancer because it doesn't have the mutational burden and doesn't seem to have as many mutations and things floating around that can be captured. However, cell-free DNA, which has the capability of measuring DNA methylation profiles, does seem to be showing some promise, and there have been some publications.  So this has also been tested in cancers of all stages and can be measured in both the plasma and in the urine. And that could be another helpful tool that needs to be validated, but that could be used to start a patient on treatment. And if the amounts of cell-free DNA went down with therapy, that could be a good indication, perhaps in advance of imaging, that a patient is doing well with therapy.  So those are some examples that I see potentially being used in the future to help direct therapy, provided that we can make these tools, that we can validate these tools, and secondly, that these tools are relatively inexpensive and that they're nimble, that they could be used right away, that it wouldn't take a long time to get the results back to help guide. Dr. Pedro Barata: For sure. I couldn't agree more. What a masterclass of all the emerging tools that are being investigated in RCC, this is fantastic.  So, I guess maybe one last question before I let you go. We have now a number of doublets, we have perhaps a triplet, if not more. If you were to guess, who do you think will be the ideal population for a triplet therapy? Some, in addition to all the tools you mentioned, maybe sarcomatoid features, etc. that might be part of the AI complement to what you mentioned earlier. But if you were to guess, do you think that 5 years from now, we're going to be offering a triplet therapy, whatever that triple therapy might be, to everybody, to certain populations? What can you tell us to help us predict what might happen in the near future to make us think about a thoughtful, shared decision-making process and try to predict who might be the ideal population for triplet therapy? Dr. Naomi Haas: So, I don't think we're going to use triplet therapy in everybody. And in fact, I hope we don't use triplet therapy in everybody because I have patients who have responded to single-agent nivolumab and remained in a continuous CR many years after they were treated that way. And I have other patients who really progressed very rapidly or relapsed very quickly after doublet therapy combinations. So, I think that what I would see in the future would be using the triplet therapy combinations in the challenging patients, the patients who we know we're not getting as far along with the doublet approach. And that's really our challenge. And I would see that perhaps some of this transcriptomics which indicates that there are subsets of renal cell carcinoma which are not going to respond well to a VEGF inhibitor or to an immune checkpoint inhibitor, that those are areas where there might be other relevant pathways where maybe the signal isn't quite as good with– maybe they have some response, but not an optimal response. And then combining another pathway into that would be a way forward to achieve a complete response in those populations.  I also want to emphasize that it may be that triplet therapy isn't the way to go, but that triplet therapy can be more of an adaptive design where a doublet therapy is started, and then the third drug, a triplet, is added at a later time. And an example of that is PDIGREE, which is the combination of ipilimumab and nivolumab. And then following imaging, patients are assigned, depending on the response, to get either cabozantinib alone, cabozantinib with nivolumab, or to continue on just nivolumab alone. And that might be a better way to address toxicity. But some of these other triplet combinations, one could also see- you could start, for example, with ipilimumab and nivolumab, and if they were having a response but you wanted to heighten the response, maybe adding the CBM-588 as an adaptive response or adding a CDK inhibitor, but sort of staggering the combination so that you spare patients some of the toxicity. So, I think all of those approaches need to be tested. Dr. Pedro Barata: That is fantastic. Dr. Haas, this is an incredible podcast. You did highlight several triplet combinations that are currently under investigation. You highlighted very, very important ongoing clinical trials. You touched base on what the future might bring as far as tools that might help us decide or optimize patient selection. We talked about adaptive designs. So really outstanding work. And also, I think this reflects the fantastic work in the manuscript that you wrote in the 2023 ASCO Educational Book.  So, thank you so much, Dr. Haas, for the incredible work that you have done and you continue to do in the GU field, and for taking the time to share your insights with us today on the ASCO Daily News Podcast. It's truly been a pleasure to chat with you today. Dr. Naomi Haas: Thank you.  Dr. Pedro Barata: Thank you again. And thank you also to our listeners for joining us today. Really happy with talking about this topic with Dr. Haas. You can also find links to the studies that we discussed today in the transcript of this episode. And 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 podcast.  So again, it has been a privilege to be here today with Dr. Haas. Thank you for joining us and have a good day.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:  Dr. Pedro Barata @PBarataMD Dr. Naomi Haas   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:  Dr. Pedro Barata: Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Dendreon Speakers' Bureau (Inst): Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.):  Blueearth, AVEO, Pfizer, Merck   Dr. Naomi Haas: Consulting or Advisory Role: Pfizer, Merck Sharp & Dohme, Calithera, Eisai, Exelisis, AVEO, Roche/Genentech Expert Testimony: Lilly

So many stars were on the stage and in the crowd. We had a hoot. Let's go through some social media content from last night's meeting and try to make sense of it all.

Congratulations to Brian Shapiro for winning a steak dinner. Thanks for answering some of our questions about radio. Artificial Intelligence joined us, Amy Tarkanian was on The Young Turks, Huge CCRCC meeting on Tuesday, Join us at Big Dogs Tavern just up the street before the meeting. We did a round up of the standard content and created a bunch of original content with the help of Richard and his AI political consultant, Bilge. I will be busy cutting up this extra long episode into YouTube clips that hopefully won't get the account a strike. The Shapiro and AI stuff need to be their own videos. Watch in double speed. Skip the parts where we were talking over the AI callers. That was a bit frustrating, but part of the process of learning new technology. Gotta break it. The OnlyFans conversation with Tiffany might be a good clip.

Featuring perspectives from Prof Laurence Albiges, Dr Toni Choueiri and Prof Thomas Powles, moderated by Dr Brian Rini, including the following topics: •      Available Data with and Ongoing Investigation of Immune Checkpoint Inhibitors for Nonmetastatic Renal Cell Carcinoma (RCC) — Prof Powles  o   Introduction (0:00) o   Case: A woman in her early 60s after left nephrectomy (T3aN0M0 clear cell carcinoma) — Swati Vishwanathan, MD (1:39) o   Cases: A man in his early 50s develops renal dysfunction after 2 cycles of adjuvant pembrolizumab for RCC and a man in his late 60s with Stage III clear cell RCC (ccRCC) discontinues adjuvant pembrolizumab due to severe musculoskeletal pain and joint swelling — Justin Peter Favaro, MD, PhD and Priya Rudolph, MD, PhD (6:05) o   Faculty presentation: Prof Powles (11:03) •      Evidence-Based Selection of First-Line Therapy for Metastatic RCC — Dr Choueiri  o   Case: A man in his early 70s with metastatic RCC enrolls on the PDIGREE trial and receives nivolumab/ipilimumab without response followed by cabozantinib — Helen H Moon, MD (21:32) o   Cases: A man in his early 70s receives ipilimumab/nivolumab for widely metastatic RCC and develops autoimmune hepatitis and a man in his early 60s with metastatic ccRCC receives ipilimumab/nivolumab followed by nivolumab with response but develops hypothyroidism and hypoadrenalism — Victoria Giffi, MD and Philip L Brooks, MD (25:33) o   Faculty presentation: Dr Choueiri (36:38) •      Treatment Options for Relapsed/Refractory RCC — Dr Rini  o   Case: A woman in her early 60s with metastatic ccRCC receives lenvatinib/pembrolizumab but develops difficult-to-manage hypertension — Eric H Lee, MD, PhD (46:04) o   Case: A woman in her mid 60s with metastatic ccRCC and somatic VHL gene mutation receives ipilimumab/nivolumab and develops a solitary brain metastasis — Sunil Gandhi, MD (52:36) o   Faculty presentation: Dr Rini (57:54) •      Management of RCC Among Special Patient Populations — Prof Albiges  o   Case: A man in his late 60s with Waldenström macroglobulinemia and metastatic papillary RCC receives first-line ipilimumab/nivolumab followed by nivolumab but develops disease progression, including brain metastases — Nikesh Jasani, MD (1:07:58) o   Case: A woman in her early 70s with a history of psoriatic arthritis develops metastatic ccRCC, receives pembrolizumab/axitinib and develops elevated liver function tests — Georges Azzi, MD (1:12:38) o   Faculty presentation: Prof Albiges (1:18:45) CME information and select publications

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530413v1?rss=1 Authors: Myszczyszyn, A., Popp, O., Kunz, S., Sporbert, A., Jung, S., Penning, L. C., Fendler, A., Mertins, P., Birchmeier, W. Abstract: Previously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established organoids from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that the organoids resembled renewal of adult kidney tubular epithelia, since organoid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-{beta}-catenin-GOF together with Notch-GOF and Wnt-{beta}-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of {beta}-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the organoid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Oncology for the Inquisitive Mind returns to its regular broadcasting schedule and discusses metastatic renal cell cancer (ccRCC). As not to be outdone, Josh takes a cultural tangent exploring the world of opera after seeing "The Hours" broadcast through Met: Live in HD. While Josh doesn't sing this episode, he highlights this opera's parallels with cancer patients undergoing treatment. To avoid losing sight of this podcast's purpose, Michael and Josh soon find their way. They discovered that metastatic renal cell carcinoma has many treatment options, including targeted therapy, immunotherapy, or even combining these two modalities! Tune in to find out where the evidence currently stands.Links to studies discussed in this episode (subscription may be required):CHECKMATE 214: https://www.nejm.org/doi/full/10.1056/nejmoa1712126KEYNOTE-426: https://www.nejm.org/doi/full/10.1056/NEJMoa1816714 Other studies of interest: CLEAR: https://www.nejm.org/doi/full/10.1056/NEJMoa2035716CheckMate 9ER: https://www.nejm.org/doi/full/10.1056/nejmoa2026982For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlexiAction: https://pixabay.com/users/alexiaction-26977400/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

This week on Oncology for the Inquisitive Mind, Michael dons his cultural hat and begins with an Ode to the Kidneys, organs that are as much a muse for poets worldwide as the heart (probably). However, you didn't come to this podcast for excellent poetry being delivered with all the panache and misguided enthusiasm of a walrus stepping on a piece of LEGO, and Michael and Josh aim to deliver on this front. Our intrepid pair examine the controversial world of adjuvant treatment of clear cell renal cell cancers (ccRCC), an area of research littered with the ghosts of negative or equivocal studies. But, not every study can be a FLAURA or a DESTINY, and negative studies are just as important, so listen on to find out exactly what NOT to do. Truly, an OftIM first!Links to studies discussed in this episode (subscription may be required):ASSURE: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591751/KEYNOTE-564: https://www.nejm.org/doi/full/10.1056/NEJMoa2106391For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlexiAction: https://pixabay.com/users/alexiaction-26977400/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Roberts Rule this episode. Kafka never wants to hear Maggie again and Tyree owns an original Dave. Jesse law kept the peace.

The Podcast Producer's Guild Premiere Tagteam was joined by Johnny Bru and Brutal Brittany to discuss censuring Republicans, shaming consultants, and defending massage parlors.

Was the latest CCRCC meeting legit? Does JP kiss and tell? Is Carl suspended for yelling at a lady at Stoney's?

It's our favorite time of the every other month. The CCRCC call to meeting.

Lots of events are coming up. You won't find out where or when here.

To obtain credit – Click Here For more information – Click Here

A recap of the CCRCC meeting. Y'all wanna get together and have breakfast?

You already know what happened in Winnemucca. Rayne Allyn Woot covered the CCRCC court filing against Carrie Buck's Zoom Club. Now Let's compare a Michele Fiore for Governor ad with one for Billionaire Sharrelle Mendenhall for CD-4.

Featuring perspectives from Dr David F McDermott, including the following topics: Introduction (0:00) Case: A woman in her early 70s with metastatic clear cell renal cell carcinoma (ccRCC) and a severe psychiatric history — Ranju Gupta, MD (10:45) Case: A man in his late 40s with metastatic ccRCC with sarcomatoid features — Laurie Matt-Amaral, MD, MPH (16:37) Case: A man in his early 60s with metastatic ccRCC — Kelly Yap, MD (29:57) Case: A man in his early 70s, a former heavy smoker, with metastatic ccRCC — Thomas Powles, MBBS, MRCP, MD (39:45) Case: A woman in her early 30s with metastatic intermediate-risk ccRCC — Prof Powles (45:41) Journal Club with David F McDermott, MD (52:58) CME information and select publications

CME credits: 0.50 Valid until: 27-08-2022 Claim your CME credit at https://reachmd.com/programs/cme/rcc-treatment-strategies-in-a-poor-risk-patient/12797/ Did you know that the current 5-year survival rate for patients diagnosed with metastatic RCC is only 12% despite advances in molecular research over the past decade? Are you familiar with recent treatment guidelines and clinical trial data showcasing the benefits of treating poor- and intermediate-risk ccRCC patients with immuno-oncology/tyrosine kinase inhibitor combination therapy? This virtual tumor board features a multidisciplinary expert panel presenting a poor-risk patient case and discussing treatment strategies and evidence-based therapy selection to optimize patient outcomes. Faculty additionally cover the importance of incorporating the patient perspective and adverse event profiles into treatment decisions. After viewing the activity, visit the Related tab for supplemental resources.

Host: Jay Raman, MD, FACS Guest: Oguz Akin, MD Guest: Robert J. Motzer, MD Guest: Elizabeth Plimack, MD, MS Did you know that the current 5-year survival rate for patients diagnosed with metastatic RCC is only 12% despite advances in molecular research over the past decade? Are you familiar with recent treatment guidelines and clinical trial data showcasing the benefits of treating poor- and intermediate-risk ccRCC patients with immuno-oncology/tyrosine kinase inhibitor combination therapy? This virtual tumor board features a multidisciplinary expert panel presenting a poor-risk patient case and discussing treatment strategies and evidence-based therapy selection to optimize patient outcomes. Faculty additionally cover the importance of incorporating the patient perspective and adverse event profiles into treatment decisions. After viewing the activity, visit the Related tab for supplemental resources.

CME credits: 0.50 Valid until: 27-08-2022 Claim your CME credit at https://reachmd.com/programs/cme/rcc-treatment-strategies-in-a-poor-risk-patient/12797/ Did you know that the current 5-year survival rate for patients diagnosed with metastatic RCC is only 12% despite advances in molecular research over the past decade? Are you familiar with recent treatment guidelines and clinical trial data showcasing the benefits of treating poor- and intermediate-risk ccRCC patients with immuno-oncology/tyrosine kinase inhibitor combination therapy? This virtual tumor board features a multidisciplinary expert panel presenting a poor-risk patient case and discussing treatment strategies and evidence-based therapy selection to optimize patient outcomes. Faculty additionally cover the importance of incorporating the patient perspective and adverse event profiles into treatment decisions. After viewing the activity, visit the Related tab for supplemental resources.

JP breaks down a few of his interactions from the CCRCC. Thank you all for chipping in on the BWC footage from the LVMPD.

Ken Minster ain't scared. He'll Zoom in to collectively scratch our heads over what could happen next in the CCRCC. Gay Republicans play football. Ian Bayne is right.

Special guest Johnny Bru joins JuggaloPatriot to learn how to "receive" the establishment when they "present" for us. The old military term is "BOHICA" or Bend Over, Here It Comes Again. Like always, it comes from the place you would least expect it. Our own producer.

The cover for issue 49 of Oncotarget features Figure 4, "CART-Tree analysis for overall survival in IMDC intermediate risk group," by Guida, et al.recently published in "Identification of international metastatic renal cell carcinoma database consortium (IMDC) intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma" which reported that as these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment. A multivariable Cox model with backward selection procedure and a Classification and Regression Tree analysis were performed to identify which prognostic factors were associated to OS in IR patients. Median OS for patients with PLT > UNL was 18 months versus 29 months for patients with normal PLT count. The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis. Elevated PLT count seems to identify a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC. Dr. Laurence Albiges from The Université Paris-Saclay said, "The risk stratification models for metastatic renal cell carcinoma (mRCC) patients were developed as clinical tool to guide counseling, to predict individual patient prognosis and also to design clinical trial." Patients lacking these negative factors have a good prognosis and may reach a longer survival; patients presenting 1 or 2 factors have an intermediate risk of death with a median overall survival about 23 months; patients with 3 or more factors have an expected poor risk outcome with median survival about 8 months. Only in the poor risk group the decision-making algorithm was different: these patients were not candidate for upfront cytoreductive nephrectomy and in selected cases could benefit of mTOR inhibitor temsirolimus in first-line setting. In the phase III trial Checkmate-214 nivolumab plus ipilimumab immunotherapy combination significantly prolonged OS versus sunitinib in intermediate and poor-risk untreated patients with mRCC. The Albiges Research Team concluded in their Oncotarget Research Paper that given the rapidly evolving field of systemic treatment in mRCC, one of the most important challenges in mRCC is how prognostic stratification will guide front-line treatment selection. Additionally characterization of heterogeneous IMDC intermediate-risk groups of patients should be seeked for optimal clinical trials design and stratification. High platelet count reflecting the cancer-related inflammatory status and seems to segregate patients with the worst prognosis in the intermediate-risk group. Further analyses are ongoing to validate these findings in patients receiving first line CPI based combination in first line. Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27762 Full text - https://www.oncotarget.com/article/27762/text/ Correspondence to - Laurence Albiges - Laurence.ALBIGES@gustaveroussy.fr Keywords - metastatic clear-cell renal cell carcinoma, IDMC, intermediate-risk, heterogeneous prognostic, platelets About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

JP does a deep dive into the Stephen Silberkraus character. Rob relives the pain of being ejected from the CCRCC meeting. Sally joins us to discuss the future of the county party.

Ejections and elections.

Chris and I tried to warn them, but now it's serious - the CCRCC and selected officers are being sued for allowing the sale of counterfeit campaign merchandise. We talk about the lawsuit, Dave's request for a retraction and apology from Chairman McDonald, and a few other tidbits that took place over the past few weeks. We also talk about some sheriffs in Virginia that are standing up for the 2nd Amendment, Sherman's logo contest, and we announce Chris "Fat" Dyer for CCRCC Community Relations Director next month!

Rob is back, and he and Chris talk about cross dressing, Chris' strange infatuation with Sherman Ray, bad debate tactics, and more. Sajdak makes yet another bonehead move by trying to piggyback off the NRCC meeting to make the CCRCC some cash, and Chris is ready to re-enlist in the Navy as long as Tulsi is his superior officer.

On Oct. 7th, 2019, the Nobel Assembly announced that William G. Kaelin, Jr., Dana-Farber Cancer Institute, shares the 2019 Nobel Prize in Physiology or Medicine with Sir Peter J. Ratcliffe of Oxford University and the Francis Crick Institute, and Gregg L. Semenza of Johns Hopkins University, for their discoveries of how cells sense and adapt to oxygen availability. In this episode Tracy interviews Hilary Nicholson, Ph.D., a postdoc research fellow in Kaelin Lab at Dana-Farber Cancer Institute. Hilary talked about her perspectives of Dr. Kaelin receiving the Nobel Prize, how Dr. Kaelin mentors and inspires her, and how her work is built upon this textbook discovery.Hilary is the first author of a recent publication on Science Signaling, "HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species". Kidney cancer is one of the top ten most common forms of cancer in developed countries, and the most common type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The von Hippel-Lindau tumor suppressor gene (VHL) inactivation is associated with ccRCC development, and hypoxia-inducible factor 2 alpha (HIF-2 alpha) is accumulated. Hilary talks about synthetic lethality between CDK4/6 inhibition and VHL loss in two species and across various human ccRCC cell lines in culture and xenografts; The study also shows that HIF-2 alpha was not required for the synthetic lethality. "These findings support testing CDK4/6 inhibitors as treatment for ccRCC, alone and in combination with HIF-2 alpha inhibitors".In addition, Hilary introduced the Science Cheer leaders, a non-profit organization comprised of 300+ current and former NFL, NBA and college cheerleaders pursuing STEM careers.  

Chris is back, and we spend an hour talking about bad campaign domain names (but campaigns are catching on), the upcoming CCRCC meeting and the various resolutions coming up, Chris' desire to have a Jesus and the money changers moment with fake Trump merchandise, an NRCC election recap, and more. We also dig into Rob's whiskey bar and sample some great Rye whiskey.

Chris and Rob ramble on for another hour about topics ranging from the upcoming NRCC elections, the Epstein "suicide", DUI mugshots, Tiffany Fung being the official representative of CCRCC, and more. Chris has a change of heart about Dave McGowan, Dave McKeon gets a nickname, and we commit to continuing on with this horrible experiment. There's some swear words. You probably shouldn't listen.

Rob Tyree hangs out with us and shares some crazy stories, while dropping some internet knowledge on us. Juggalo Patriot makes an appearance to discuss the CCRCC meeting. Its really a good episode, so stick around til the end.

Rob Tyree hangs out with us and shares some crazy stories, while dropping some internet knowledge on us. Juggalo Patriot makes an appearance to discuss the CCRCC meeting. Its really a good episode, so stick around til the end.

Dr Ari Hakimi of the Memorial Sloan-Kettering Cancer Center, New York, USA, at the ASCO GU congress 2014 discusses the MET variant as a prognostic marker in clear cell renal cell carcinoma (ccRCC) and its future implications.

DaveMcKeon wants a bio about Chris before he'll come on the show. Normally people take our invitations with enthusiasm. This is not how we start a relationship with the party we want to be the chairman of. Twitter stuff. Joe Heck breakfast stuff.

CCRCC...guns. James Smack flip flops. Trek Wars. More Steven Brooks nonsense.

David's beauty pageant. Steven Brooks is crazy. We are all actors. CCRCC meeting tomorrow. Music talk. We set a record for most "Jesus" mentions.

Oh No! JP gets to write the description that no one reads! We feud with celebrities...or at least we try to. CCRCC Election numbers. Underground music talk with our new best friend TheOfficialJRoy. Kim.com and Gangnam Style. That's all you need to know!

Sopa... sopa cabanna.... hottest spot in.... oh you know how it goes... Sending love to the republican party with a bit of internet piracy.