ROUNDTABLE D ISCUSSION Pivotal CABOSUN Trial Reshapes Treatment Options For Intermediate, Poor-RISK RCC Robert A. Figlin, MD Toni Choueiri, MD Gisela Schwab, MD T his Roundtable discussion focuses on results from CABOSUN, a pivotal clinical trial and how data emerging from it could reshape the treatment landscape in kidney cancer. The moderator is Robert A. Figlin, MD, Editor-in-Chief of the Kidney Cancer Journal. The discussion includes Toni Choueiri, MD, Principal Investigator for METEOR, and Gisela Schwab, MD, Chief Medical Officer of Exelixis, a biopharmaceutical company focused on developing and commercializing small molecule therapies with the potential to improve the treatment of cancer. The company is the developer of cabozantinib. Dr Figlin: The pivotal trial has demonstrated both a PFS and survival advantage in the second line treatment of RCCa. How should the practicing oncologist use these data to determine whom to offer this treatment? Dr Choueiri: The pivotal phase 3 study METEOR demonstrated significant improvements in overall survival, progression free survival and objective response rate with cabozantinib as compared to everolimus. The results were clinically meaningful and consistently favored (Table) cabozantinib across multiple prespecified and post-hoc sub-group analyses indicating benefit across all patient subgroups regardless of prognostic risk, extent of disease, prior VEGFR TKI regimen, MET status, or age. The safety profile was generally similar to that observed with other TKIs which target VEGFR. We presented and published the results of METEOR 2015 and 20161,2. Dr Schwab: These results led to regulatory approval of Cabometyx (cabozantinib) by the FDA in April 2016 and by the EMA in September 2016. Cabometyx is a new stan- Keywords: CABOSUN, cabozantinib, sunitinib, METEOR, VEGF, TKI. Address for reprints and correspondence: Douglas Clary,Douglas Clary, PhD, Executive Director, Medical Affairs, Exelixis, 210 E. Grand Ave., South San Francisco, CA 94080 dclary@exelixis.com 130 Kidney Cancer Journal dard of care for RCC patients after prior anti-angiogenic therapy and can be offered to this patient population. Dr Figlin:With other recently approved agents in the second line setting of RCCa (Opdivo, lenvatinib/everolimus) we need to describe how to assist the practicing oncologist in choosing between these recently approved agents in this setting. Dr Choueiri: Both Cabometyx and Opdivo showed significant improvements in overall survival and response rate in their privotal trials in previously-treated RCC patients. However, Cabometyx demonstrated significant improvements in all three key efficacy endpoints of overall survival, progression-free survival and objective response rate, making it the only agent showing consistent benefit across all three key efficacy endpoints in a large randomized phase 3 study. Lenvatinib in combination with everolimus was studied in a smaller randomized phase 2 trial in which the combination showed significantly improved PFS and objective response rate, and improved OS compared with everolimus. All three agents have achieved regulatory approval. However, the strength of evidence for Cabometyx and Opdivo resulted in a preferred NCCN category 1 recommendation. This means that patients and physicians have several treatment options without a clear front-runner, as none of these therapies has been compared in a head-tohead trial. Dr Figlin: With the CABOSUN data evolving would you describe the study design and results and whether cabozantinib should be a consideration for the upfront treatment in RCCa? Dr Schwab: CABOSUN is a randomized phase 2 trial comparing cabozantinib and sunitinib in the front-line treatment of patients with intermediate or poor risk RCC. CABOSUN was conducted by the Alliance for Clinical Tri
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