We present an exploratory post hoc analysis from the phase 3 CheckMate 214 trial of first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) without prior nephrectomy and with an evaluable primary tumor, a population under-represented in clinical trials. Patients with clear cell aRCC were randomized to NIVO+IPI every 3 wk for four doses followed by NIVO monotherapy, or sunitinib every day for 4 wk (6-wk cycle). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and primary tumor shrinkage were assessed. PFS and ORR were assessed per independent radiology review committee using RECIST version 1.1. With minimum study follow-up of 4 yr for intent-to-treat patients, OS favored NIVO+IPI (n = 53) over sunitinib (n = 55; hazard ratio 0.63, 95% confidence interval 0.40-1.0) among patients without prior nephrectomy. ORR was higher (34% vs 15%; p = 0.0041) and median duration of response was longer with NIVO+IPI versus sunitinib (20.5 vs 14.1 mo); the best overall response was partial response in either arm. A ≥30% reduction in the diameter of intact target renal tumors was achieved in 35% of patients with NIVO+IPI versus 20% with sunitinib. Safety was consistent with the global study population. In conclusion, in patients with aRCC without prior nephrectomy and with an evaluable primary tumor, NIVO+IPI showed survival benefits and renal tumor reduction versus sunitinib. This trial is registered at ClinicalTrials.gov as NCT02231749. PATIENT SUMMARY: In an exploratory analysis of a large global trial (CheckMate 214), we observed positive outcomes (both survival and tumor response to treatment) with nivolumab plus ipilimumab over sunitinib in a subgroup of patients with advanced kidney cancer who did not undergo removal of their primary kidney tumor. This subset of patients represents a population that has not been studied in clinical trials and for whom outcomes with new immunotherapy combination regimens are not yet known. We conclude that treatment with nivolumab plus ipilimumab offers these patients a survival benefit versus sunitinib, consistent with that observed in the overall study, as well as a notable kidney tumor reduction.
European urology. 2021 Nov 05 [Epub ahead of print]
Laurence Albiges, Nizar M Tannir, Mauricio Burotto, David McDermott, Elizabeth R Plimack, Philippe Barthélémy, Camillo Porta, Thomas Powles, Frede Donskov, Saby George, Christian K Kollmannsberger, Howard Gurney, Marc-Oliver Grimm, Yoshihiko Tomita, Daniel Castellano, Brian I Rini, Toni K Choueiri, David Leung, Shruti Shally Saggi, Chung-Wei Lee, M Brent McHenry, Robert J Motzer
Department of Cancer Medicine, Gustave Roussy, Villejuif, France. Electronic address: ., Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bradford Hill Clinical Research Center, Santiago, Chile., Division of Medical Oncology, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA., Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Medical Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., University of Pavia, Pavia, Italy., Department of Urology, Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust, London, UK., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA., Department of Medicine, British Columbia Cancer Agency, Vancouver, Canada., Department of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, Australia., Department of Urology, Jena University Hospital, Jena, Germany., Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain., Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Department of Imaging, Bristol Myers Squibb, Princeton, NJ, USA., Department of Clinical Trials, Bristol Myers Squibb, Princeton, NJ, USA., Department of Biostatistics, Bristol Myers Squibb, Princeton, NJ, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.