Podcasts about Everolimus

N Engl J Med 2019;381:1411-1421Background Percutaneous coronary intervention (PCI) had been clearly established as the standard of care for ST elevation myocardial infarction. Yet many patients taken for PCI have multiple lesions in addition to the culprit. The benefit of routinely treating additional significant lesions has been unclear, with previous smaller trials showing reductions in composite outcomes primarily driven by reduced revascularization rates.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The COMPLETE (Complete vs Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial investigated whether performing percutaneous coronary intervention (PCI) on non-culprit lesions reduces cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease.Patients The trial enrolled 4,041 patients from 140 centers in 31 countries between February 2013 and March 2017. Eligible patients had STEMI with successful culprit-lesion PCI and at least one non-culprit coronary artery lesion with ≥70% stenosis (or 50-69% stenosis with FFR ≤0.80) in a vessel ≥2.5mm in diameter. Patients were randomized within 72 hours after successful culprit-lesion PCI. Exclusion criteria included planned surgical revascularization and previous coronary bypass surgery.Baseline Characteristics The mean age was approximately 62 years, with about 80% being male. Approximately 19% had diabetes, 8% had previous MI, and 7% had previous PCI. Over 90% of patients underwent primary PCI (vs. pharmacoinvasive or rescue PCI), with 80% using radial access.The groups were well-balanced, with similar SYNTAX scores at baseline and similar culprit and non-culprit lesion characteristics. About 76% had one residual diseased vessel and 24% had two or more. Guideline directed medical therapy was robust and balanced, including more than 99% on dual antiplatelet therapy, 98% on statins, 88% on beta blocker, and 85% on ACEi or ARB.In patients in the complete revascularization group designated for non-culprit PCI during index hospitalization, the mean time to PCI was 1 day. In the group designated for non-culprit PCI after discharge, the mean time was 23 days.Trial procedures Patients were randomized to complete revascularization (n=2,016) or culprit-lesion-only PCI (n=2,025). In the complete revascularization group, investigators specified before randomization whether non-culprit PCI would occur during index hospitalization or after discharge (within 45 days).Everolimus-eluting stents were recommended for all procedures. Both groups received guideline-based medical therapy including dual antiplatelet therapy with aspirin and ticagrelor for at least one year.Endpoints The first coprimary outcome was cardiovascular death or new myocardial infarction. The second coprimary outcome was cardiovascular death, myocardial infarction, or ischemia-driven revascularization. Secondary outcomes included individual components of the composite outcomes, all-cause mortality, and safety outcomes like major bleeding, stroke, and stent thrombosis.Trialists estimated that a sample of 4000 patients would give 80% power to detect a 22% lower risk of the composite of cardiovascular death or myocardial infarction in the complete-revascularization group than in the culprit-lesion-only PCI group, assuming an event rate of 5% per year in the culprit-lesion-only PCI group. The first coprimary outcome was tested at a P value of 0.045 and the second at a P value of 0.0119.The co-primary endpoints were analyzed according to the time to first event approach. Confidence intervals for secondary and exploratory efficacy outcomes were not adjusted for multiple comparisons, and therefore inferences drawn from these intervals may not be reproducible.Results Over a median follow-up of 36.2 months, the first coprimary outcome occurred in 7.8% of the complete-revascularization group versus 10.5% of the culprit-lesion-only group (hazard ratio 0.74, 95% CI: 0.60-0.91; p= 0.004). Benefit was driven by reduced myocardial infarction rates (5.4% vs 7.9%) while cardiovascular death rates were similar (2.9% vs 3.2%).The second coprimary outcome was also reduced with complete revascularization (8.9% versus 16.7%, HR: 0.51, 95% CI: 0.43-0.61; p

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Alok Khorana, a GI medical oncologist from the Cleveland Clinic, to discuss the latest highlights from the GI ASCO 2025 conference. We dive into four key studies that are practice-informing and potentially practice-changing: 1. BREAKWATER: We explore the implications of using Encorafenib and Cetuximab in combination with FOLFOX for patients with BRAF V600E mutations, which are associated with poor prognosis. 2. CheckMate-8HW: This study investigates whether dual checkpoint inhibition is more effective than single-agent immunotherapy for MSI-high patients, revealing promising results in progression-free survival. 3. Aspirin in Adjuvant Settings: We discuss the role of low-dose aspirin in reducing recurrence rates for patients with PI3K alterations, highlighting its potential as a practice-changing intervention. 4. STARTER-NET: Finally, we review the findings from the study on Everolimus combined with Lanreotide for neuroendocrine tumors, noting the lack of overall survival benefit. Tune in for an insightful discussion on these important topics in oncology, and learn how these findings could impact treatment strategies in your practice. Don't forget to like, subscribe, and check out our other episodes for more conference highlights and treatment discussions! YouTube: https://youtu.be/YOToz3hKYTg Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers #OncologyBrothers #GIASCO2025 #ColorectalCancer #Immunotherapy #NeuroendocrineTumors #CancerResearch #Podcast

In this episode, listen to Virginia Kaklamani, MD, DSc; Erica L. Mayer, MD, MPH; and Laura M. Spring, MD, share their clinical insights and takeaways from a live symposium, including from key abstracts presented at the 2024 San Antonio Breast Cancer Symposium:Estrogen Receptor Mutations in Patients With HR-Positive/HER2-Negative Advanced Breast CancerCurrent Guideline Recommendations for When to Pursue ESR1 Mutation Testing Mutations in Patients With HR-Positive/HER2-Negative Advanced Breast CancerChoice and Sequencing of Next Line of Systemic Therapy for ESR1-Mutated Advanced Breast Cancer Based on Tumor Molecular AlterationsOverview of Class-Related and Unique Adverse Events With Approved and Emerging Oral SERDSExpert Recommendations for the Management of Oral SERDs-Related Adverse EventsProgram faculty:Virginia Kaklamani, MD, DScProfessor of MedicineRuth McLean Bowman Bowers Chair in Breast Cancer Research and TreatmentA.B. Alexander Distinguished Chair in Oncology LeaderBreast Oncology ProgramUT Health San AntonioMD Anderson Cancer CenterSan Antonio, TexasErica L. Mayer, MD, MPHDirector of Breast Cancer Clinical ResearchDana-Farber Cancer InstituteAssociate Professor in MedicineHarvard Medical SchoolBoston, MassachusettsLaura M. Spring, MDBreast Medical OncologistMass General Hospital Cancer CenterHarvard Medical SchoolBoston, Massachusetts Resources:To download the slides associated with this podcast discussion, please visit the program page.

N Engl J Med 2010;362:1663-74.Background: The RAVEL and TAXUS-IV trials compared the sirolimus- and paclitaxel-eluting 2nd generation stents to 1st generation bare metal stents. Both trials reported improvements in surrogate endpoints - “in-stent luminal loss” was the primary endpoint of RAVEL and “ischemia-driven target-vessel revascularization” was the primary endpoint of TAXUS-IV. Neither trial showed differences in hard endpoints like death or MI but were not powered for such events.The observation that restenosis still occurred with 2nd generation stents drove interest in developing newer stent technology with improved bioavailability and drug delivery. The 3rd generation everolimus-eluting stent was felt to represent such a development but like its predecessors had only been tested in experiments using surrogate endpoints that were not driven by clinical symptoms. Thus, the SPIRIT IV trial sought to test the hypothesis that 3rd generation everolimus-eluting stents would reduce patient-driven clinical outcomes compared 2nd generation paclitaxel-eluting stents. Furthermore, it was designed to be large enough to provide data on important subgroups, especially patients with diabetes.Patients: Limited details are provided about inclusion and exclusion criteria in the main manuscript and readers are directed to a previous publication and supplemental appendix. Lesion characteristics had to be less than 28 mm in length with a reference-vessel diameter between 2.5 to 3.75 mm. Patients were excluded if they had features making them complex from either a clinical or angiographic standpoint. *Note to learners: Be especially skeptical of trials that do not include at least an abridged version of important inclusion and exclusion criteria in the main publication manuscript. This often indicates that the criteria are complex and that patients are highly selected, which limits the generalizability of the findings to routine practice. Baseline characteristics: The average age of patients was 63 years and 68% were men. Approximately 32% of patients had diabetes with about one quarter being insulin-dependent. Over 20%of patients smoked and a similar percentage had a previous heart attack.Three quarters of patients had 1 target lesion, 22% had 2 target lesions and 3% had 3 and 11% of patients had 1 or more complex lesions. The average lesion length was 15 mm, reference-vessel diameter was 2.75 mm, minimal luminal diameter was 0.75 mm, and average % stenosis was 72%.Procedures: Patients were randomized in a 2:1 ratio to receive an everolimus- or paclitaxel-eluting stent. They were stratified based on having diabetes or not, whether they had a single or complex lesion, and study site. Operators were not blind to the stent being used. At least 300 mg of aspirin was administered before catheterization and at least 300 mg of clopidogrel was recommended before the procedure and was required within 1 hour after stent implantation. Patients took at least 80 mg of aspirin daily for an indefinite period and 75 mg of clopidogrel for at least 12 months. Clinical follow-up visits were scheduled at 30, 180, 270, and 365 days and yearly through 5 years.Endpoints: The primary end point was ischemia-driven target lesion failure at 1 year defined by the composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization. As was the case in the TAXUS-IV trial, “ischemia-driven” did not necessarily mean “symptom-driven”. Two major secondary endpoints were also prespecified which included ischemia-driven target-lesion revascularization and the composite of death or target-vessel MI.The trial was powered for sequential testing of noninferiority and superiority for both the primary and 2 major secondary endpoints. The criteria for noninferiority would be met if the upper limit of the 97.5% confidence interval was not more than 3.1%. This was based on an assumed 1 year target-lesion failure rate of 8.2% for both groups. The trial had 90% power to show non-inferiority. Superiority testing was prespecified if the criterion for noninferiority was met. It was estimated that 3690 patients would have 90% power to detect a 2.9% absolute reduction in the primary end point, at a two-sided alpha of 0.05. The trial also had 90% power to test noninferiority for ischemia-driven target-lesion revascularization and the composite of cardiac death or target-vessel MI at a 2.1% margin. It had 90% and 91% power to test for superiority of these endpoints if noninferiority was met.*Note to learners: The statistical analysis plan for this trial demonstrates 2 important concepts in hypothesis testing. First, trials can be powered in a prespecified manner for non-inferiority and superiority testing. Second, trials can be powered for prespecified hypothesis testing of more than just a single endpoint.Results: Patients were enrolled over a 2 year period from 66 U.S. sites. There were a total of 3,687 patients included in the final analysis with 2,458 in the everolimus-eluting stent group and 1,229 in the paclitaxel-eluting stent group. There were some significant differences for patients receiving everolimus-eluting stents that included the number of stents per lesion, total stent length per lesion, the ratio of stent length to lesion length and the maximum pressure used.At 1 year, everolimus-eluting stents met non-inferiority for the primary and major secondary endpoints and met superiority for 2 of 3. Everolimus-eluting stents reduced the primary endpoint of target-lesion failure (4.2% vs 6.8%; RR 0.62; 95% CI 0.46 to 0.82) and the major secondary endpoint of ischemia-driven target lesion revascularization (2.5 vs 4.6%; RR 0.55; 95% CI 0.38 to 0.78) but not the other major secondary endpoint of cardiac death or target-vessel MI (2.2% vs 3.2%; RR 0.69; 95% CI 0.46 to 1.04). Differences in target-lesion failure were driven by statistically significant reductions in target-lesion revascularization (2.5% vs 4.6%) as well as MI (1.9% vs 3.1%) but not all-cause (1.0% vs 1.3%) or cardiac death (0.4% vs 0.4%). Stent thrombosis was also significantly reduced but rates were very low in both groups and the trial was not powered for this endpoint.Interestingly, subgroup analysis of the primary endpoint revealed a statistically significant interaction for treatment efficacy in patients with diabetes such that diabetics did not appear to benefit from everolimus-eluting stents (6.4% vs 6.9%) compared to non-diabetics (3.3% vs 6.7%; p for interaction = 0.02).Conclusions: In patients with stable CAD who underwent generally non-complex PCI procedures, 3rd generation everolimus-eluting stents compared to 2nd generation paclitaxel-eluting stents reduced a composite endpoint of ischemia-driven target-lesion failure by 38% with a number needed to treat of approximately 40 patients. This was associated with statistically significant reductions in nonfatal MI with a NNT of approximately 100 patients and ischemia-driven target lesion revascularization with a NNT of approximately 50 patients. Everolimus-eluting stents did not reduce death.There was an interaction noted for diabetic patients who did not appear to significantly benefit from everolimus-eluting stents. Notably, diabetics exhibited more severe angiographic disease with a higher prevalence of multivessel disease, diffuse plaque burden, and a greater likelihood of left main coronary artery involvement. This subgroup finding along with the highly selected nature of the study cohort reduces our confidence that the 3rd generation everolimus-eluting stent confers significant advantages over 2nd generation stents for many patients who receive them in clinical practice.One final consideration is that the trial was single blinded and operators were aware of stent type which could have biased their performance and the study results.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Interview with Alexander T. Hillel, MD, author of Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis: A Phase 1 Nonrandomized Clinical Trial. Hosted by Paul C. Bryson, MD, MBA. Related Content: Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis

Interview with Alexander T. Hillel, MD, author of Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis: A Phase 1 Nonrandomized Clinical Trial. Hosted by Paul C. Bryson, MD, MBA. Related Content: Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis

Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Oncotarget papers based on the number of times a DOI is successfully resolved. Below are Crossref's Top 10 Oncotarget DOIs published in 2023. 10: Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC) DOI: https://doi.org/10.18632/oncotarget.28355 Authors: Md Maksudul Alam, Janmaris Marin Fermin, Mark Knackstedt, Mackenzie J. Noonan, Taylor Powell, Landon Goodreau, Emily K. Daniel, Xiaohua Rong, Tara Moore-Medlin, Alok R. Khandelwal, and Cherie-Ann O. Nathan 9: Novel inflammation-combined prognostic index to predict survival outcomes in patients with gastric cancer DOI: https://doi.org/10.18632/oncotarget.28353 Authors: Noriyuki Hirahara, Takeshi Matsubara, Shunsuke Kaji, Hikota Hayashi, Yohei Sasaki, Koki Kawakami, Ryoji Hyakudomi, Tetsu Yamamoto, and Yoshitsugu Tajima 8: Crosstalk between triple negative breast cancer and microenvironment DOI: https://doi.org/10.18632/oncotarget.28397 Authors: Karly Smrekar, Artem Belyakov and Kideok Jin 7: Systemic AL amyloidosis: current approach and future direction DOI: https://doi.org/10.18632/oncotarget.28415 Authors: Maroun Bou Zerdan, Lewis Nasr, Farhan Khalid, Sabine Allam, Youssef Bouferraa, Saba Batool, Muhammad Tayyeb, Shubham Adroja, Mahinbanu Mammadii, Faiz Anwer, Shahzad Raza, and Chakra P. Chaulagain 6: Deciphering the mechanisms of action of progesterone in breast cancer DOI: https://doi.org/10.18632/oncotarget.28455 Authors: Gaurav Chakravorty, Suhail Ahmad, Mukul S. Godbole, Sudeep Gupta, Rajendra A. Badwe, and Amit Dutt 5: Targeting cellular respiration as a therapeutic strategy in glioblastoma DOI: https://doi.org/10.18632/oncotarget.28424 Authors: Enyuan Shang, Trang Thi Thu Nguyen, Mike-Andrew Westhoff, Georg Karpel-Massler, and Markus D. Siegelin 4: Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells DOI: https://doi.org/10.18632/oncotarget.28382 Author: Mikhail V. Blagosklonny, M.D., Ph.D. 3: The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy DOI: https://doi.org/10.18632/oncotarget.28354 Authors: Anqi Shao and David M. Owens 2: Genomic landscape of metastatic breast cancer (MBC) patients with methylthioadenosine phosphorylase (MTAP) loss DOI: https://doi.org/10.18632/oncotarget.28376 Authors: Maroun Bou Zerdan, Prashanth Ashok Kumar, Elio Haroun, Nimisha Srivastava, Jeffrey Ross, and Abirami Sivapiragasam 1: Using cancer proteomics data to identify gene candidates for therapeutic targeting DOI: https://doi.org/10.18632/oncotarget.28420 Authors: Diana Monsivais, Sydney E. Parks, Darshan S. Chandrashekar, Sooryanarayana Varambally, and Chad J. Creighton Oncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com. Oncotarget is indexed/archived on MEDLINE / PMC / PubMed. For media inquiries, please contact media@impactjournals.com.

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. 

Polymer-Free Amphilimus-Eluting Stents vs. Biodegradable-Polymer Everolimus-Eluting Stents in All-Comers Undergoing PCI: 1-Year Results of the PARTHENOPE Trial

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.18.533275v1?rss=1 Authors: DeSpenza, T., Kiziltug, E., Allington, G., Barson, D., O'Connor, D., Robert, S. M., Mekbib, K. Y., Nanda, P., Greenberg, A., Singh, A., Duy, P. Q., Mandino, F., Zhao, S., Lynn, A., Reeves, B. C., Marlier, A., Getz, S. A., Nelson-Williams, C., Shimelis, H., Zhang, J., Walsh, L. K., Wang, W., Smith, H., OuYang, A., Deniz, E., Lake, E., Jin, S. C., Luikart, B. W., Kahle, K. T. Abstract: Expansion of the cerebrospinal fluid (CSF)-filled cerebral ventricles (ventriculomegaly) is the quintessential feature of congenital hydrocephalus (CH) but also seen in autism spectrum disorder (ASD) and several neuropsychiatric diseases. PTEN is frequently mutated in ASD; here, we show PTEN is a bona fide risk gene for the development of ventriculomegaly, including neurosurgically-treated CH. Pten-mutant hydrocephalus is associated with aqueductal stenosis due to the hyperproliferation of periventricular Nkx2.1+ neural precursors (NPCs) and CSF hypersecretion from inflammation-dependent choroid plexus hyperplasia. The hydrocephalic Pten-mutant cortex exhibits ASD-like network dysfunction due to impaired activity of Nkx2.1+ NPC-derived inhibitory interneurons. Raptor deletion or post-natal Everolimus corrects ventriculomegaly, rescues cortical deficits, and increases survival by antagonizing mTORC1-dependent Nkx2.1+ cell pathology. These results implicate a dual impact of PTEN mutation on CSF dynamics and cortical networks via the dysregulation of NPCs and their interneuron descendants. These data identify a non-surgical treatment target for hydrocephalus and have implications for other developmental brain disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new research paper was published in Oncotarget's Volume 14 on February 2, 2023, entitled, “Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC).” TP53 mutant head and neck squamous cell carcinoma (HNSCC) patients exhibit poor clinical outcomes with 50–60% recurrence rates in advanced stage patients. In a recent phase II clinical trial, adjuvant therapy with everolimus (mTOR inhibitor) significantly increased 2-year progression-free survival in p53 mutated patients. TP53-driven mTOR activation in solid malignancies causes upregulation of HIF-1α and its target, downstream effector VEGF, by activating STAT3 cell signaling pathway. In this recent study, researchers Md Maksudul Alam, Janmaris Marin Fermin, Mark Knackstedt, Mackenzie J. Noonan, Taylor Powell, Landon Goodreau, Emily K. Daniel, Xiaohua Rong, Tara Moore-Medlin, Alok R. Khandelwal, and Cherie-Ann O. Nathan from LSU-Health Sciences Center investigated the effects of everolimus on the STAT3/HIF-1α/VEGF pathway in TP53 mutant cell lines and xenograft models. “The role of mTOR inhibitors (mTORi) as potent growth inhibitory and antiangiogenic/anti-lymphangiogenic agents in HNSCC is well established [18]. Moreover, mTORi significantly suppressed baseline invasiveness of endothelial and HNSCC tumor cells [19]. However, the underlying molecular mechanisms for mutant p53 protein-mediated activation of the mTOR pathway which drive the oncologic processes in HNSCC are yet to be elucidated.” Treatment with everolimus significantly inhibited cell growth in vitro and effectively reduced the growth of TP53 mutant xenografts in a minimal residual disease (MRD) model in nude mice. Everolimus treatment was associated with significant downregulation of STAT3/HIF-1α/VEGF pathway in both models. Further, treatment with everolimus was associated with attenuation in tumor angiogenesis and lymphangiogenesis as indicated by decreased microvessel density of vascular and lymphatic vessels in HN31 and FaDu xenografts. Everolimus downregulated the STAT3/HIF-1α/VEGF pathway to inhibit growth and in vitro tube formation of HMEC-1 (endothelial) and HMEC-1A (lymphatic endothelial) cell lines. “Our studies demonstrated that everolimus inhibits the growth of TP53 mutant tumors by inhibiting angiogenesis and lymphangiogenesis through the downregulation of STAT3/HIF-1α/VEGF signaling.” DOI: https://doi.org/10.18632/oncotarget.28355 Correspondence to: Cherie-Ann O. Nathan - cherieann.nathan@lsuhs.edu Keywords: TP53 mutant, HNSCC, angiogenesis, everolimus, mTOR About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube 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

Drs Sumanta Pal and Martin Voss discuss second-line treatment of renal cell carcinoma, including current studies and agents used in the refractory setting. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968745). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma Treatment & Management https://emedicine.medscape.com/article/281340-treatment Comparative Effectiveness of Axitinib Versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61613-9/fulltext Cabozantinib Versus Everolimus in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/NEJMoa1510016 CANTATA: Primary Analysis of a Global, Randomized, Placebo (Pbo)-Controlled, Double-Blind Trial of Telaglenastat (CB-839) + Cabozantinib Versus Pbo + Cabozantinib in Advanced/Metastatic Renal Cell Carcinoma (mRCC) Patients (pts) Who Progressed on Immune Checkpoint Inhibitor (ICI) or Anti-Angiogenic Therapies. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4501 FDA Approves Tivozanib for Relapsed or Refractory Advanced Renal Cell Carcinoma https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma (TIVO-3): A Phase 3, Multicentre, Randomised, Controlled, Open-Label Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30735-1/fulltext Lenvatinib, Everolimus, and the Combination in Patients With Metastatic Renal Cell Carcinoma: A Randomised, Phase 2, Open-Label, Multicentre Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment (CONTACT-03) https://clinicaltrials.gov/ct2/show/NCT04338269 TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients With Metastatic Renal Cell Carcinoma https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(20)42472-X Kidney Cancer Research Summit https://kcrs.kidneycan.org/

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

Chris Ryan describes the results of this adjuvant study. 

Today we bring back our popular Journal Club with a Fellow segment. We're joined by Dr. Karine Tawagi of the Oschner Clinic in Louisiana to discuss the CLEAR trial: "Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma" as published in the New England Journal of Medicine. CLEAR: doi.org/10.1056/NEJMoa2035716 Back us on Patreon! www.patreon.com/plenarysession Check out our YouTube channel: www.youtube.com/channel/UCUibd0E2kdF9N9e-EmIbUew

Commentary by Dr. Valentin Fuster

Discussion on lenvatinib and everolimus prior to the CLEAR trial presentation.

C. Michael Gibson and Hiroki Shiomi look at long-term outcomes from RESET.

This week we explore the world of cardiac transplantation with particular emphasis on the Fontan patient and transplantation. Outcomes are improving rapidly. Why is this? What about the liver and how are decisions made regarding cardiac versus cardiac+hepatic transplantation in this patient population? We review all of these questions with world authority on cardiac transplantation Dr. Daphne Hsu, Professor of Pediatrics, Chief of Pediatric Cardiology and Interim Chair of Pediatrics at Montefiore - Albert Einstein College of Medicine. Her insights into this complex patient group are valuable and novel. Article reviewed: DOI: 10.1016/j.athoracsur.2016.08.110

This week we explore the world of cardiac transplantation with particular emphasis on the Fontan patient and transplantation. Outcomes are improving rapidly. Why is this? What about the liver and how are decisions made regarding cardiac versus cardiac+hepatic transplantation in this patient population? We review all of these questions with world authority on cardiac transplantation Dr. Daphne Hsu, Professor of Pediatrics, Chief of Pediatric Cardiology and Interim Chair of Pediatrics at Montefiore - Albert Einstein College of Medicine. Her insights into this complex patient group are valuable and novel. Article reviewed: DOI: 10.1016/j.athoracsur.2016.08.110

Commentary by Dr. Valentin Fuster

Interview with Wayne Batchelor, MD, author of Outcomes in Women and Minorities Compared With White Men 1 Year After Everolimus-Eluting Stent Implantation: Insights and Results From the PLATINUM Diversity and PROMUS Element Plus Post-Approval Study Pooled Analysis, and Ajay J Kirtane, MD, SM, author of Race/Ethnicity–Based Outcomes in Cardiovascular Medicine

Dr Larkin talks to ecancertv at ASCO 2015 about the results of a randomised phase II trial of kinase inhibitor lenvatinib used in combination with everolimus in renal cell carcinoma, which saw significant improvements in progression free survival compared with everolimus alone.

Dr Kornblum presents results at the San Antonio Breast Cancer Symposium 2016 from a randomised, double-blind phase II trial of everolimus vs placebo in combination with fulvestrant from HR /HER- metastatic breast cancer for patients resistant of aromatase inhibitor therapy. The addition of everolimus doubled median PFS to 10.4 months, with adverse events at a higher, but manageable, severity, consistent with previous assessment of everolimus in the BOLERO-2 trial.

Dr Kornblum speaks with ecancer at the San Antonio Breast Cancer Symposium 2016 about results from the PrECOG 0102 trial, a randomised, double-blind phase II trial of everolimus vs placebo in combination with fulvestrant from HR /HER- metastatic breast cancer for patients resistant of aromatase inhibitor therapy. He describes that the addition of everolimus doubled median PFS to 10.4 months, with adverse events at a higher, but manageable, severity, consistent with previous assessment of everolimus in the BOLERO-2 trial.

Dr. Stephen Ellis and Dr. C. Michael Gibson Discuss

Dr Choueiri speaks with ecancertv at ASCO 2016 about results from METEOR, a randomised phase III trial of cabozantinib for patients with advanced renal cell carcinoma (RCC), compared to everolimus. Cabozantinib displayed a significant impact on previously treated patients, improving median overall survival from 16.5 months in the everolimus arm to 21.4 months for cabozantinib, and a 33% reduction in the rate of death He also highlights the scale of the trial, from the international team gathering data to the impact on standard of care in RCC.

Dr Escudier talks to ecancertv at ASCO GU 2016 about how patients with advanced kidney cancer live for nearly twice as long without their disease progressing if they are treated with cabozantinib, a small molecule tyrosine kinase inhibitor (TKI) that targets c-MET, VEGFR2 and AXL. In the interview he discusses the results of the open-label METEOR trial, which compared the TKI against everolimus, a standard of care in mRCC. The METEOR trial met its primary endpoint of improved progression free survival, and subgroup analyses of the endpoints progression free survival and overall response rate generally favoured cabozantinib over everolimus in patients with advanced RCC.

mTOR-Inhibitoren (Synonym: Rapamycin) sind Wirkstoffe, die sowohl in der Immunsuppression als auch in der antiproliferativen Therapie systemisch und lokal Verwendung finden. In Vorversuchen unserer Arbeitsgruppe mit Zellkulturen zeigte sich schnell ein großes Adsorptionspotential von Rapamycin – beziehungsweise von dessen Derivat Everolimus – an die Oberflächen von Zellkulturflaschen. Diese Adsorption hängt im Wesentlichen von zwei Faktoren ab: dem Proteingehalt des Mediums und der spezifischen Oberfläche der Zellkulturflaschen. Um dies zu zeigen, wurden verschiedene gebräuchliche Zellkulturflaschen (Nunclon, Ultra-low-attachment, Weichglas, unbehandelte Polystyren-Oberflächen und Polystyren Oberflächen beschichtet mit Collagen 1 beziehungsweise Poly-D-Lysin) sowie Duranglas-Petrischalen ausgewählt. Die Oberflächen der Zellkulturflaschen wurden eine Stunde mit Medium mit einer definierten Menge an Everolimus bedeckt, gespült und wiederum eine Stunde mit DMSO bedeckt. DMSO löst die Substanz wieder von der Oberfläche ab. Die Everolimuskonzentrationen im Medium nach einer Stunde und in der DMSO-Lösung wurden mittels LC-MS/MS bestimmt. Es zeigte sich signifikante Adsorption von Everolimus in absteigender Reihenfolge: Ultra-low-attachment > Unbehandeltes Polystyren > Collagen 1 > Nunclon > Poly-D Lysin > Weichglas > Duranglas (bei 10% FCS in Medium) und Ultra-low-attachment > Unbehandelt > Collagen 1 > Weichglas > Poly-D-Lysin > Duranglas (bei 30% FCS in Medium). Im Folgeversuch wurden vier der Zellkulturflaschen ausgewählt (Nunclon, Unbehandelt, Collagen 1, Duranglas-Petrischalen) und untersucht, ob die reine Adsorption von Everolimus an die Oberfläche ohne Everolimus im Medium negative Effekte auf das Zellwachstum hat. Dies konnte bei drei Zelllinien (293T, VSMC, HUVEC) mittels Zellzählung demonstriert werden. Bei allen drei Zelllinien wurden p-p70s6K- Western Blots durchgeführt. Die p-p70s6K ist ein downstream gelegenes Phosphorylierungsprodukt von mTOR, welches wiederum von Rapamycin/ Everolimus gehemmt wird. Teilweise zeigte sich hier eine absteigende Phosphorylierung. Bei HUVEC- Zellen wurde zusätzlich die Expression von VEGF und p-p70s6K mittels ELISA untersucht. VEGF ist ein Faktor, der Wachstumssignale spezifisch an Gefäß- Endothelzellen vermittelt. Hier konnte entgegen der Erwartungen sogar eine Zunahme der Expression mit steigender Everolimuskonzentration gemessen werden. Neuere Studien legen jedoch nahe, dass VEGF nicht ausschließlich über TOR aktiviert wird. Bei p-p70s6K zeigte sich die erwartete Abnahme der Expression. Die Versuche weisen auf eine signifikante Beeinflussung des Zellwachstums durch Everolimusadsorption an Oberflächen hin. Inwiefern sich Adsorption bei Zellversuchen mit Everolimus in Lösung auswirkt, ist noch unklar. Eine Minderung der Everolimuswirkung wäre denkbar. Um die Oberflächenadsorption bei Versuchen mit Everolimus möglichst gering zu halten, empfiehlt unsere Arbeitsgruppe anhand der Versuchsergebnisse die Kultivierung auf wenig absorbierenden Oberflächen wie Duranglas beziehungsweise die Erhöhung der FCS-Konzentration in Lösung, soweit von den Zellen toleriert.

Commentary by Dr. Valentin Fuster

Prof James Yao - University of Texas MD Anderson Cancer Center, Houston, USA Dr Yao talks to ecancertv at ECC 2015 about the use of everolimus in the treatment of advanced, progressive neuroendocrine tumours of the gastrointestinal tract and lung, particularly in those that are non-functional. During the interview he discusses the results of the phase III RADIANT-4 trial that showed a 2.8-fold increase in progression-free survival with everolimus over placebo from 3.9 to 11 months. Data are not yet mature for overall survival but show a trend for an improvement with everolimus, he says.

Commentary by Dr. Valentin Fuster

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Dr. Guru Sonpavde highlights the top research news in immunotherapy for kidney cancer from the ASCO 2014 Annual Meeting.

Dr. Guru Sonpavde highlights the top research news in immunotherapy for kidney cancer from the ASCO 2014 Annual Meeting.

Dr. Guru Sonpavde highlights the top research news in immunotherapy for kidney cancer from the ASCO 2014 Annual Meeting.

Cometriq (cabozantinib) is already approved for thyroid cancer and is showing promise for late stage kidney cancer.

Cometriq (cabozantinib) is already approved for thyroid cancer and is showing promise for late stage kidney cancer.

Cometriq (cabozantinib) is already approved for thyroid cancer and is showing promise for late stage kidney cancer.

Dr. Lauren Harshman explains what PD1 (an immune T-cell) and PDL1 (a protein on the PD1 T-cell) are and how new drugs impact them to fight kidney cancer.

Dr. Lauren Harshman explains what PD1 (an immune T-cell) and PDL1 (a protein on the PD1 T-cell) are and how new drugs impact them to fight kidney cancer.

Dr. Lauren Harshman explains what PD1 (an immune T-cell) and PDL1 (a protein on the PD1 T-cell) are and how new drugs impact them to fight kidney cancer.

Drugs in early stage clinical trials seem to show benefit for non-clear cell kidney cancer, but more trials must take place and patients are desperately needed to enroll in them.

Drugs in early stage clinical trials seem to show benefit for non-clear cell kidney cancer, but more trials must take place and patients are desperately needed to enroll in them.

Drugs in early stage clinical trials seem to show benefit for non-clear cell kidney cancer, but more trials must take place and patients are desperately needed to enroll in them.

Dr. Guru Sonpavde discusses what he does when he first begins treating a patient recently diagnosed with late stage kidney cancer.

Dr. Guru Sonpavde discusses what he does when he first begins treating a patient recently diagnosed with late stage kidney cancer.

Dr. Guru Sonpavde discusses what he does when he first begins treating a patient recently diagnosed with late stage kidney cancer.

Editor's Audio Summary by Howard Bauchner, MD, Editor in Chief of JAMA, the Journal of the American Medical Association, for the July 02, 2014 issue

Results from recent clinical trials looking into PD1 inhibitors of kidney cancer are giving patients and doctors reasons to be hopeful.

Results from recent clinical trials looking into PD1 inhibitors of kidney cancer are giving patients and doctors reasons to be hopeful.

Results from recent clinical trials looking into PD1 inhibitors of kidney cancer are giving patients and doctors reasons to be hopeful.

Tue, 1 Oct 2013 12:00:00 +0100 https://epub.ub.uni-muenchen.de/24018/1/oa_24018.pdf Kozlik-Feldmann, Rainer; Netz, Heinrich; Engmann, Roxana; Fuchs, Alexandra Th; Birnbaum, Julia; Kohler, Sarah M.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to second line treatment of kidney cancer.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to second line treatment of kidney cancer.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA describes optimal management of kidney cancer that is confined to the kidney, including surgery and the role of any additional post-surgical treatment. 

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA describes optimal management of kidney cancer that is confined to the kidney, including surgery and the role of any additional post-surgical treatment. 

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA describes optimal management of kidney cancer that is confined to the kidney, including surgery and the role of any additional post-surgical treatment. 

Background: Everolimus is approved for treatment of anti-vascularendothelial growth factor (VEGF)-refractory patients with metastaticrenal cell carcinoma (mRCC). Clinical trials rarely mirror treatmentreality. Thus, a broader evaluation of everolimus is valuable forroutine use. Patients and Methods: A German multicenternon-interventional study documented mRCC patients starting everolimusafter failure of initial VEGF-targeted therapy. Primary endpoint waseffectiveness, defined as time to progression (TIP) according toinvestigator assessment (time from first dose to progression). Results:Of 382 documented patients, 196 were included in this interim analysis.

A new analysis may help doctors identify breast cancer patients who will benefit from treatment with the immune suppressant drug everolimus, said French researchers at the 4th IMPAKT Breast Cancer Conference in Brussels, Belgium. Everolimus is currently used as an immunosuppressant to prevent patients rejecting transplanted organs and in the treatment of renal cell cancer. Research is also being conducted into the drug’s use in other cancers, including breast cancer. Dr Thomas Bachelot, from Centre Leon Berard in Lyon and colleagues analyzed data from the TAMRAD study, published two years ago

Audio Journal of Cardiovascular Medicine Bioabsorbable Everolimus-Eluting Stent: 6-Month Angiographic and IVUS Results REFERENCE: Abstract 2402-3, American College of Cardiology New Orleans PATRICK SERRUYS, Erasmus University, Rotterdam COMMENT: SPENCER KING, Piedmont Hospital, Atlanta Six-months follow-up of patients receiving a new bioabsorbable drug-eluting stent are favourable, according to Patrick Serruys whose group has been investigating the stent which elutes everolimus in a group of 30 patients. During the ACC Annual Meeting in New Orleans he discussed with Peter Goodwin the potential benefits the new device can bring to coronary patients.

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel.