Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial.

The extent to which response and survival benefits with immunotherapy-based regimens persist informs optimal first-line treatment options. We provide long-term follow-up in patients with advanced renal cell carcinoma (aRCC) receiving first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the phase 3 CheckMate 214 trial. Survival, response, and safety outcomes with NIVO+IPI versus SUN were assessed after a minimum of 42 months of follow-up.

Patients with aRCC were enrolled from October 16, 2014, through February 23, 2016. Patients stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and region were randomized to nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for four doses, followed by nivolumab (3 mg/kg) every 2 weeks; or SUN (50 mg) once per day for 4 weeks (6-week cycle). Primary endpoints: overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) per independent radiology review committee in IMDC intermediate-risk/poor-risk patients. Secondary endpoints: OS, PFS, and ORR in the intention-to-treat (ITT) population and safety. Favorable-risk patient outcomes were exploratory.

Among ITT patients, 550 were randomized to NIVO+IPI (425 intermediate/poor risk; 125 favorable risk) and 546 to SUN (422 intermediate/poor risk; 124 favorable risk). Among intermediate-risk/poor-risk patients, OS (HR, 0.66; 95% CI, 0.55-0.80) and PFS (HR, 0.75; 95% CI, 0.62-0.90) benefits were observed, and ORR was higher (42.1% vs 26.3%) with NIVO+IPI versus SUN. In ITT patients, both OS benefits (HR, 0.72; 95% CI, 0.61-0.86) and higher ORR (39.1% vs 32.6%) were observed with NIVO+IPI versus SUN. In favorable-risk patients, HR for death was 1.19 (95% CI, 0.77-1.85) and ORR was 28.8% with NIVO+IPI versus 54.0% with SUN. Duration of response was longer (HR, 0.46-0.54), and more patients achieved complete response (10.1%-12.8% vs 1.4%-5.6%) with NIVO+IPI versus SUN regardless of risk group. The incidence of treatment-related adverse events was consistent with previous reports.

NIVO+IPI led to improved efficacy outcomes versus SUN in both intermediate-risk/poor-risk and ITT patients that were maintained through 42 months' minimum follow-up. A complete response rate >10% was achieved with NIVO+IPI regardless of risk category, with no new safety signals detected in either arm. These results support NIVO+IPI as a first-line treatment option with the potential for durable response.


Journal for immunotherapy of cancer. 2020 Jul [Epub]

Robert J Motzer, Bernard Escudier, David F McDermott, Osvaldo Arén Frontera, Bohuslav Melichar, Thomas Powles, Frede Donskov, Elizabeth R Plimack, Philippe Barthélémy, Hans J Hammers, Saby George, Viktor Grünwald, Camillo Porta, Victoria Neiman, Alain Ravaud, Toni K Choueiri, Brian I Rini, Pamela Salman, Christian K Kollmannsberger, Scott S Tykodi, Marc-Oliver Grimm, Howard Gurney, Raya Leibowitz-Amit, Poul F Geertsen, Asim Amin, Yoshihiko Tomita, M Brent McHenry, Shruti Shally Saggi, Nizar M Tannir

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA ., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Department of Medicine, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA., Centro de Investigación Clínica Bradford Hill, Santiago, Chile., Department of Oncology, Palacky University, and University Hospital Olomouc, Olomouc, Czech Republic., Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, UK., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA., Department of Medical Oncology, Hôpitaux Universitaires de Strasbourg / ICANS, Strasbourg, France., Division of Hematology and Oncology, UT Southwestern Kidney Cancer Program, Dallas, Texas, USA., Divisions of Medical Oncology and Urology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA., Interdisciplinary Genitourinary Oncology, West German Cancer Center Essen, Essen, Germany., Department of Internal Medicine, University of Pavia, Pavia, Italy., Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel., Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France., Department of Medical Oncology, Dana-Farber Cancer Institute, The Lank Center for Genitourinary Oncology, Boston, Massachusetts, USA., Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA., Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile., Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada., Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington, USA., Department of Urology, Jena University Hospital, Jena, Germany., Department of Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia., Oncology Institute, Shamir Medical Center, Be'er Yaakov, Israel., Department of Oncology, Herlev Hospital, Copenhagen, Denmark., Department of Medical Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA., Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.