Nivolumab+ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years median follow-up from CheckMate 214.
Patients with aRCC (N=1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. Endpoints included OS, and independent radiology review committee-assessed progression-free survival (PFS) and objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients.
With 8 years (99.1 months) median follow-up, the HR (95% CI) for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all IMDC risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). Median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1-not estimable (NE) versus 19.8-33.2; ITT], 82.8 versus 19.8 months [54.1-NE versus 16.4-26.4; I/P], and 61.5 versus 33.2 months [27.8-NE versus 24.8-51.4; FAV]). Incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, those receiving subsequent therapy based on their response status, clinical subpopulations, and adverse events over time.
Superior survival, durable response benefits, and a manageable safety profile were maintained with NIVO+IPI versus SUN at 8 years, the longest phase III follow-up for a first-line checkpoint inhibitor combination therapy in aRCC.
Annals of oncology : official journal of the European Society for Medical Oncology. 2024 Aug 02 [Epub ahead of print]
N M Tannir, L Albigès, D F McDermott, M Burotto, T K Choueiri, H J Hammers, P Barthélémy, E R Plimack, C Porta, S George, F Donskov, M B Atkins, H Gurney, C K Kollmannsberger, M-O Grimm, C Barrios, Y Tomita, D Castellano, V Grünwald, B I Rini, R Jiang, H Desilva, V Federov, C-W Lee, R J Motzer
University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: ., Gustave Roussy, Villejuif, France., Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA., Bradford Hill Clinical Research Center, Santiago, Chile., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA., UT Southwestern Kidney Cancer Program, Dallas, TX., Medical Oncology Unit, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Fox Chase Cancer Center, Philadelphia, PA., University of Pavia, Pavia, Italy., Roswell Park Cancer Institute, Buffalo, NY., Aarhus University Hospital, Aarhus, Denmark; University Hospital of Southern Denmark, Esbjerg, Denmark., Georgetown Lombardi Comprehensive Cancer Center, Washington, DC., Department of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, New South Wales, Australia., British Columbia Cancer Agency, Vancouver, BC, Canada., Jena University Hospital and Comprehensive Cancer Center Central Germany (CCCG), Campus Jena, Jena, Germany., Hospital São Lucas, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil., Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Medical Oncology Department University Hospital 12 de Octubre, CIBER-ONC, Madrid, Spain., Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, West-German Cancer Center Essen, University Hospital Essen, Essen, Germany., Vanderbilt University Medical Center, Nashville, TN., Bristol Myers Squibb, Princeton, NJ., Memorial Sloan Kettering Cancer Center, New York, NY.