Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial.

To report updated analyses of the phase III CheckMate 214 trial with extended minimum follow-up assessing long-term outcomes with first-line nivolumab plus ipilimumab (NIVO+IPI) versus (vs) sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC).

Patients with aRCC with a clear cell component were stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk and randomised to NIVO (3 mg/kg) plus IPI (1 mg/kg) every three weeks ×4 doses, followed by NIVO (3 mg/kg) every two weeks; or SUN (50 mg) once per day ×4 weeks (6-week cycle). Efficacy endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) per independent radiology review committee in patients with intermediate/poor-risk disease (I/P; primary), intent-to-treat patients (ITT; secondary) and in patients with favourable-risk disease (FAV; exploratory).

Overall, 1096 patients were randomised (ITT: NIVO+IPI, n=550, SUN, n=546; I/P: NIVO+IPI, n=425, SUN, n=422; FAV: NIVO+IPI, n=125, SUN, n=124). After 4 years minimum follow-up, OS (HR; 95% CI) remained superior with NIVO+IPI vs SUN in ITT (0.69; 0.59 to 0.81) and I/P patients (0.65; 0.54 to 0.78). Four-year PFS probabilities were 31.0% vs 17.3% (ITT) and 32.7% vs 12.3% (I/P), with NIVO+IPI vs SUN. ORR remained higher with NIVO+IPI vs SUN in ITT (39.1% vs 32.4%) and I/P (41.9% vs 26.8%) patients. In FAV patients, the HRs (95% CI) for OS and PFS were 0.93 (0.62 to 1.40) and 1.84 (1.29 to 2.62); ORR was lower with NIVO+IPI vs SUN. However, more patients in all risk groups achieved complete responses with NIVO+IPI: ITT (10.7% vs 2.6%), I/P (10.4% vs 1.4%) and FAV (12.0% vs 6.5%). Probability (95% CI) of response ≥4 years was higher with NIVO+IPI vs SUN (ITT, 59% (0.51 to 0.66) vs 30% (0.21 to 0.39); I/P, 59% (0.50 to 0.67) vs 24% (0.14 to 0.36); and FAV, 60% (0.41 to 0.75) vs 38% (0.22 to 0.54)) regardless of risk category. Safety remained favourable with NIVO+IPI vs SUN.

After long-term follow-up, NIVO+IPI continues to demonstrate durable efficacy benefits vs SUN, with manageable safety.

ClinicalTrials.gov identifier: NCT02231749.

ESMO open. 2020 Nov [Epub]

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, Shruti Shally Saggi, M Brent McHenry, Robert J Motzer

Department of Cancer Medicine, Gustave Roussy, Villejuif, France ., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Bradford Hill Clinical Research Center, Santiago, Chile., Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA., Medical Oncology Unit, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., University of Bari 'A. Moro', Bari, Italy., Department of Urology, Barts Cancer Institute, Royal Free NHS Trust, London, UK., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA., Department of Medicine, British Columbia Cancer Agency, Vancouver, British Columbia, Canada., Department of Medical Oncology, Westmead Hospital, Westmead, New South Wales, Australia., Department of Urology, Jena University Hospital, Jena, Thüringen, Germany., Niigata University Faculty of Medicine 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, Tennessee, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Department of Clinical Trials, Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Biostatistics, Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

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