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Medical Crossfire®: Renal Cell Carcinoma in an Era of Rapid Discovery: Key Questions - PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap



1 of 3
PER Pulse Recap

Resistance to TKI and Immunotherapy for Renal Cell Carcinoma

Medical Crossfire®: RCC in an Era of Rapid Discovery: Key Questions featured nationally recognized experts in renal cell carcinoma (RCC). Program chair Robert Figlin, MD, along with faculty, David McDermott; Robert Motzer, MD; and Elizabeth Plimack, MD, discussed challenges encountered by clinicians treating patients with RCC, exchanged perspectives and suggestions for optimizing care, and reviewed current and emerging standards of care in RCC.

This first of 3 PER Pulse™ Recaps from this Medical Crossfire® focuses on mechanisms of innate and acquired resistance to therapies for RCC:

  • Of patients with advanced RCC, 10% to 20% exhibit primary resistance to frontline sunitinib therapy.
  • The primary driver of resistance to sunitinib or other anti-VEGF tyrosine kinase inhibitors (TKI) targeted agents has not been fully elucidated.
  • Targets of newer TKIs being used in RCC include pathways postulated to be important in resistance (eg, cabozantinib targeting of AXL and MET and lenvatinib targeting of FGFR), a hypothesis supported by the clinical activity of these 2 agents among patients with RCC who were previously treated with sunitinib or sorafenib.
  • Approximately one-third of patients with advanced RCC who receive a programmed cell death protein 1 (PD-1) inhibitor exhibit innate resistance. Upon microscopic analysis, tumors of these patients typically are not infiltrated by T cells.
  • T-cell–infiltrated kidney tumors are more likely to respond to a PD-1 inhibitor than noninfiltrated tumors.
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  • Most patients will eventually need an additional therapy beyond PD-1 inhibition; the mechanisms behind this acquired resistance to PD-1-blocking therapy are unknown.

For more on this discussion, visit www.gotoper.com



2 of 3
PER Pulse™ Recap

Overall Survival and Subgroup Data for New Agents in RCC

Medical Crossfire®: RCC in an Era of Rapid Discovery: Key Questions featured nationally recognized experts in renal cell carcinoma (RCC). Program chair Robert Figlin, MD, along with faculty, David McDermott; Robert Motzer, MD; and Elizabeth Plimack, MD, discussed challenges encountered by clinicians treating patients with RCC, exchanged perspectives and suggestions for optimizing care, and reviewed current and emerging standards of care in RCC.

This second of 3 PER Pulse™ Recaps from this Medical Crossfire® focuses on a panel discussion of overall survival outcomes and subgroup analysis data from randomized trials of new agents in RCC. Below are some points of discussion from this expert panel:

  • In a subgroup analysis of data from a randomized trial of cabozantinib versus everolimus, cabozantinib provided superior benefit among all patient subgroups examined. Dr. Plimack noted that among the patients with the most worrisome disease characteristics (eg, highest risk, tumor burden, number of sites of metastasis), the benefits observed with cabozantinib versus everolimus were proportionally better than the benefits observed among patients with a lower risk, lower tumor burden, or fewer involved sites.
  • It is important to explain to patients that at this time, second-line therapeutic decision making is more about which drug to choose next versus selecting one drug over another.
  • The panel is encouraged by data that approximately one-third of patients from the original phase II trial of nivolumab for advanced RCC beyond first-line therapy remain alive at 4 years of follow-up.
  • Single-agent programmed cell death protein 1 (PD-1) inhibition can provide long-term benefit; however, a small percentage of these patients maintained a remission after the discontinuation of nivolumab, with most eventually receiving subsequent therapy.
  • Achieving durable remission (benefit that lasts months after discontinuation of therapy) with a PD-1 inhibitor may require a yet-to-be-determined combination regimen.

For more on this discussion, visit www.gotoper.com


3 of 3
PER Pulse™ Recap

Will Emerging Data from ESMO Change Your Practice?

Medical Crossfire®: RCC in an Era of Rapid Discovery: Key Questions featured nationally recognized experts in renal cell carcinoma (RCC). Program chair Robert Figlin, MD, along with faculty, David McDermott; Robert Motzer, MD; and Elizabeth Plimack, MD, discussed challenges encountered by clinicians treating patients with RCC, exchanged perspectives and suggestions for optimizing care, and reviewed current and emerging standards of care in RCC.

This third of 3 PER Pulse™ Recaps from this Medical Crossfire® focuses on panel discussion of data from the CABOSUN and S-TRAC trials, which evaluated frontline cabozantinib and adjuvant sunitinib, presented at ESMO 2016. Below are some key points of discussion from this expert panel:

  • The randomized, phase II, multicenter, Alliance A031203 CABOSUN trial randomized 157 patients with poor- or intermediate-risk RCC to frontline cabozantinib or sunitinib (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.46-0.95; one-sided P = .012). Results from this study, first presented at ESMO 2016 and later published in the Journal of Clinical Oncology, demonstrated improved progression-free survival with cabozantinib versus sunitinib.
  • The potential availability of cabozantinib as a first-line agent raise new questions about therapeutic selection and sequencing in the frontline setting and beyond.
  • The randomized, double-blind, phase III S-TRAC trial randomized 615 patients with locoregional, high-risk, clear-cell RCC to receive adjuvant sunitinib or placebo. Disease-free survival in the sunitinib arm was superior to that of placebo arm (HR, 0.76; 95% CI, 0.59-0.98; P = 0.03).
  • The results of the S-TRAC trial came as a surprise to many oncologists because of the negative results of the double-blind, placebo-controlled, randomized, phase III ASSURE trial. In ASSURE, patients with RCC were randomized to receive adjuvant sunitinib, sorafenib, or placebo.
  • Dr. Motzer pointed out that key differences in the designs of the S-TRAC versus ASSURE trials may explain the discordant results.
  • The faculty agreed that they look forward to the results of ongoing adjuvant TKI trials in RCC (eg, ATLAS and PROTECT) that are expected to be released in the coming year.
  • Dr. McDermott speculated whether the mechanism of action of VEGF TKIs provides a clear rationale for their use in the adjuvant setting and noted that although the benefits observed in S-TRAC were clinically meaningful, they would need to be carefully weighed against the potential toxicity burdens.

For more on this discussion, visit www.gotoper.com

PER® Practice Pulse
Practice Pattern Questions
How often do you attend society oncology/hematology meetings? (ASCO, ASH, SABCS)
Practice Pattern Questions
What is the most significant barrier to implementing new information in your clinical practice?






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