Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18. 1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score.
Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability.
Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN.
After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC.
ClinicalTrials.gov, NCT03141177.
ESMO open. 2024 Apr 19 [Epub ahead of print]
T Powles, M Burotto, B Escudier, A B Apolo, M T Bourlon, A Y Shah, C Suárez, C Porta, C H Barrios, M Richardet, H Gurney, E R Kessler, Y Tomita, J Bedke, S George, C Scheffold, P Wang, V Fedorov, R J Motzer, T K Choueiri
Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, London; Royal Free National Health Service Trust, London, UK. Electronic address: ., Bradford Hill Clinical Research Center, Santiago, Chile., Gustave Roussy, Villejuif, France., Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA., Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., MD Anderson Cancer Center, Houston, USA., Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Department of Internal Medicine, University of Pavia, Pavia, Italy., Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Latin American Cooperative Oncology Group, Porto Alegre, Brazil., Fundación Richardet Longo, Instituto Oncológico de Córdoba, Córdoba, Argentina., Westmead Hospital and Macquarie University, Westmead and Sydney, Australia., Division of Medical Oncology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, USA., Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany., Roswell Park Comprehensive Cancer Center, Buffalo., Exelixis, Inc., Alameda., Bristol Myers Squibb, Princeton., Memorial Sloan Kettering Cancer Center, New York., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston; Brigham and Women's Hospital, Harvard Medical School, Boston, USA.