Practice-Changing Data - The Phase III KEYNOTE-564 Study and more from ASCO 2021
August 02, 2021
PEER-TO-PEER CLINICAL CONVERSATION
KEYNOTE-564 Demonstrates Improvement in Disease-Free Survival - A New Standard of Care for High-Risk Kidney Cancer
Rana McKay, MD
Rana McKay joins Alicia Morgans in a discussion on the potential paradigm shift in the treatment landscape for high-risk kidney cancer with the findings from the KEYNOTE-564 trial. Dr. McKay was the discussant in the plenary session at the 2021 ASCO meeting following the presentation of the results by Toni Choueiri. The phase 3 KEYNOTE-564 trial is a randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of pembrolizumab in the adjuvant treatment setting of renal cell carcinoma after nephrectomy.
Highlights from the 2021 American Society of Clinical Oncology Annual Meeting
Pembrolizumab Versus Placebo as Post-Nephrectomy Adjuvant Therapy for Patients with Renal Cell Carcinoma: Randomized, Double-Blind, Phase III KEYNOTE-564 Study
Toni K. Choueiri, MD
Toni Choueiri presented results of the KEYNOTE-564 trial evaluating pembrolizumab versus placebo as adjuvant therapy for patients with RCC. Adjuvant pembrolizumab post nephrectomy demonstrated a statistically significant and clinically meaningful improvement in DFS versus placebo in patients with intermediate-high, high risk, or M1 no evidence RCC.
Results from the KEYNOTE-564 Study of Adjuvant Pembrolizumab in Resected Clear-Cell Renal Cell Carcinoma (RCC)
Rana R. McKay, MD
Rana McKay discussed late-breaking abstract 5, results from the KEYNOTE-564 (KN-564) study of adjuvant pembrolizumab in resected clear-cell renal cell carcinoma (RCC). Dr. McKay suggested that these findings are potentially practice-changing. First, this is the first positive phase 3 study of immunotherapy in RCC demonstrating improved disease-free survival with less toxicity than other previously trialed agents like sunitinib. Much work remains to be done, including confirmation of an overall survival benefit, consideration of whether this can be used in other RCC histologies, and what the implications of adjuvant pembrolizumab would be for treatment choices in advanced RCC.
So Your Patient with Kidney or Bladder Cancer Responded to Immunotherapy: What's Next?
Immunotherapy as Curative Therapy in Advanced Kidney and Bladder Cancer: Fantasy or Reality?
Thomas Powles, MD
The Plenary agenda of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting included a session, entitled “So Your Patient with Kidney or Bladder Cancer Responded to Immunotherapy: What's Next?”. In this context, Tom Powles discussed whether we can consider immunotherapy a truly curative approach for patients with advanced kidney and bladder cancer.
Practical Considerations for the Treatment of Patients on Long-term Immunotherapy
Mamta Parikh, MD, MS
The Plenary agenda of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting included a session, entitled “So Your Patient with Kidney or Bladder Cancer Responded to Immunotherapy: What's Next?”. In this context, Dr. Mamta Parikh from UC Davis Comprehensive Cancer Center discussed considerations for the treatment of patients who respond well to immunotherapy and are on therapy for a long time.
Temporal Characteristics of Treatment-Emergent Adverse Events and Dose Modifications with Tivozanib and Sorafenib in the Phase 3 TIVO-3 Study of Relapsed or Refractory mRCC
Sumanta Kumar Pal, MD
Sumanta Pal presented secondary analyses of the TIVO-3 trial focused on the temporal characteristics of treatment-emergent adverse events (TEAEs) to enable proactive supportive care strategies and improve patient experience.
Nivolumab Plus Cabozantinib in Patients With Non-Clear Cell Renal Cell Carcinoma: Results of a Phase 2 Trial
Chung-Han Lee, MD, Ph.D.
Chung-Han Lee presented results of a phase II trial of nivolumab and cabozanitinb in patients with non-clear cell renal cell carcinoma. The combination of cabozantinib and nivolumab had an acceptable safety profile and showed promising efficacy in patients with metastatic non-clear cell RCC with papillary, unclassified, or translocation associated histology whereas activity was not observed in patients with chromophobe RCC.
Cabozantinib Exposure-Response Analysis for the Phase 3 CheckMate 9ER Trial of Nivolumab Plus Cabozantinib Versus Sunitinib in First-Line Advanced Renal Cell Carcinoma
Amishi Y. Shah, MD
Amishi Shah presented an exposure-response analysis of cabozantinib exposure on efficacy and safety outcomes within the context of the CheckMate 9ER trial. Based on exposure-response modeling of patients receiving first line combination therapy with nivolumab and cabozantinib for advanced RCC in the CheckMate 9ER trial, cabozantinib exposure was not significantly associated with PFS, though higher cabozantinib exposure was associated with higher rates of PPE and diarrhea.
Safety and Efficacy Outcomes with Nivolumab plus Ipilimumab in Patients with Advanced Renal Cell Carcinoma and Brain Metastases: Results from the CheckMate 920 Trial
Hamid Emamekhoo, MD
Hamid Emamekhoo and colleagues presented updated safety and efficacy results for the cohort of patients with advanced RCC of any histology and brain metastases from CheckMate 920. Results from the CheckMate 920 trial add to the limited evidence and relative dearth of prospective or retrospective analyses that had evaluated outcomes in patients with RCC and brain metastases, a population with poor prognosis and a high unmet medical need.
Survival Benefit of Nephrectomy Prior to Immunotherapy-Based Combinations in Patients with Metastatic Renal Cell Carcinoma: An FDA Pooled Analysis
Jaleh Fallah, MD
Jaleh Fallah and colleagues presented the results of their study assessing the correlation between nephrectomy prior to immunotherapy-based combination therapies and overall survival (OS) in patients with de novo metastatic RCC.
Unanswered Questions in the Management of Advanced Renal Cell Carcinoma
Anil Kapoor, MD, FRCSC
Anil Kapoor addressing unanswered questions in the management of advanced renal cell carcinoma. Dr. Kapoor notes that there are many unanswered questions. Dr. Kapoor discussed are attempting to answer several of these questions highlighting that given the complex nature of advanced kidney cancer management, decisions regarding cytoreductive nephrectomy should ideally be made in a multidisciplinary setting.
Pembrolizumab Versus Investigator’s Choice of Paclitaxel, Docetaxel, or Vinflunine in Recurrent, Advanced Urothelial Cancer: 5-Year Follow-up from the Phase 3 KEYNOTE-045 Trial
Joaquim Bellmunt, MD, Ph.D.
Joaquim Bellmunt presented updated results from the KEYNOTE-045 trial after >5 years of follow-up since the last patient was randomized. These data are consistent with the primary analysis and with the 2- and 3-year follow-up analyses that led to the approval of pembrolizumab for treatment of advanced platinum-resistant or platinum-refractory urothelial carcinoma irrespective of PD-L1 status.
PrE0807: A Phase Ib Feasibility Trial of Neoadjuvant Nivolumab Without or with Lirilumab in Cisplatin-Ineligible Patients with Muscle-Invasive Bladder Cancer
Petros Grivas, MD, Ph.D.
Petros Grivas presented the results of this phase Ib trial PrE0807. This is a phase Ib multi-institutional trial in patients with localized muscle-invasive bladder cancer treated with two neoadjuvant doses (4 weeks apart) of nivolumab alone (480 mg) in cohort 1 or nivolumab (480 mg) + lirilumab (240 mg) in cohort 2 prior to radical cystectomy without adjuvant therapy.
A Phase 3, Multicenter, Randomized Study Evaluating the Efficacy of TAR-200 in Combination with Cetrelimab Versus Concurrent Chemoradiotherapy in Participants with Muscle-Invasive Urothelial Carcinoma of the Bladder
Stephen B. Williams, MD, MS, FACS
Stephen Williams and colleagues presented the trial design for this phase 3 trial evaluating whether combination treatment with intravesical TAR-200 and systemic cetrelimab will result in enhanced local and systemic antitumor activity versus concurrent chemoradiotherapy.
Neoadjuvant Atezolizumab with Gemcitabine and Cisplatin in Patients with Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase 2 Trial
Samuel A. Funt, MD
Samuel Funt presented the results of a trial testing the combination of Atezolizumab with Gemcitabine and Cisplatin in a phase II trial among patients with muscle-invasive bladder cancer. This study of met its primary endpoint with 27 of 39 patients (69%) with muscle-invasive bladder cancer achieving <pT2N0 at radical cystectomy, including (44%) achieving pT0N0.
A Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Advanced Renal Cell Carcinoma With Bone Metastases (RADICAL/Alliance A031801)
Rana R. McKay, MD
Rana McKay presented the rationale and design for the RADICAL trial of radium-223 dichloride and cabozantinib in patients with mRCC and bone metastases. The study was activated in December 2019 and accrual is currently ongoing throughout the NCTN.