Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial

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 Fedorov; C-W Lee; R J Motzer

doi:10.1016/j.annonc.2024.07.727

Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial

Ann Oncol. 2024 Aug 2:S0923-7534(24)01516-3. doi: 10.1016/j.annonc.2024.07.727. Online ahead of print.

Authors

N M Tannir¹, L Albigès², D F McDermott³, M Burotto⁴, T K Choueiri⁵, H J Hammers⁶, P Barthélémy⁷, E R Plimack⁸, C Porta⁹, S George¹⁰, F Donskov¹¹, M B Atkins¹², H Gurney¹³, C K Kollmannsberger¹⁴, M-O Grimm¹⁵, C Barrios¹⁶, Y Tomita¹⁷, D Castellano¹⁸, V Grünwald¹⁹, B I Rini²⁰, R Jiang²¹, H Desilva²², V Fedorov²³, C-W Lee²⁴, R J Motzer²⁵

Affiliations

¹ Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: ntannir@mdanderson.org.
² Department of Medical Oncology (Département de Médecine Oncologique), Gustave Roussy, Villejuif, France.
³ Division of Medical Oncology, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, USA.
⁴ Department of Oncology, Bradford Hill Clinical Research Center, Santiago, Chile.
⁵ Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston.
⁶ Department Internal Medicine, UT Southwestern Kidney Cancer Program, Dallas, USA.
⁷ Department of Medical Oncology, Medical Oncology Unit, Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
⁸ Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, USA.
⁹ Department of Internal Medicine, University of Pavia, Pavia, Italy.
¹⁰ Department of Medicine, Roswell Park Cancer Institute, Buffalo, USA.
¹¹ Department of Oncology, Aarhus University Hospital, Aarhus; University Hospital of Southern Denmark, Esbjerg, Denmark.
¹² Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.
¹³ Department of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, Australia.
¹⁴ Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
¹⁵ Department of Urology, Jena University Hospital and Comprehensive Cancer Center Central Germany (CCCG), Campus Jena, Jena, Germany.
¹⁶ Department of Internal Medicine and Oncology Research Center, Hospital São Lucas, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
¹⁷ Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
¹⁸ Medical Oncology Department, University Hospital 12 de Octubre, CIBER-ONC, Madrid, Spain.
¹⁹ Interdisciplinary Genitourinary Oncology, Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, West-German Cancer Center Essen, University Hospital Essen, Essen, Germany.
²⁰ Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville.
²¹ Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton.
²² Late Clinical Development, Bristol Myers Squibb, Princeton.
²³ Oncology Late Clinical Development, Bristol Myers Squibb, Princeton.
²⁴ Department of Clinical Trials, Bristol Myers Squibb, Princeton.
²⁵ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.

PMID: 39098455
DOI: 10.1016/j.annonc.2024.07.727

Abstract

Background: Nivolumab plus 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 of median follow-up from CheckMate 214.

Patients and methods: 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. The endpoints included OS, independent radiology review committee (IRRC)-assessed progression-free survival (PFS), and IRRC-assessed objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients.

Results: With 8 years (99.1 months) of median follow-up, the hazard ratio [HR; 95% confidence interval (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 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). The median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1 months-not estimable (NE) versus 19.8-33.2 months] in ITT patients, 82.8 versus 19.8 months (54.1 months-NE versus 16.4-26.4 months) in I/P patients, and 61.5 versus 33.2 months (27.8 months-NE versus 24.8-51.4 months) in FAV patients. The 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.

Conclusions: 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.

Keywords: CheckMate 214; Nivolumab, ipilimumab; advanced renal cell carcinoma; dual checkpoint inhibition; long-term follow-up; phase III.