Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial

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

doi:10.1016/j.esmoop.2024.102994

Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial

ESMO Open. 2024 Apr 19;9(5):102994. doi: 10.1016/j.esmoop.2024.102994. Online ahead of print.

Authors

T Powles¹, M Burotto², B Escudier³, A B Apolo⁴, M T Bourlon⁵, A Y Shah⁶, C Suárez⁷, C Porta⁸, C H Barrios⁹, M Richardet¹⁰, H Gurney¹¹, E R Kessler¹², Y Tomita¹³, J Bedke¹⁴, S George¹⁵, C Scheffold¹⁶, P Wang¹⁷, V Fedorov¹⁷, R J Motzer¹⁸, T K Choueiri¹⁹

Affiliations

¹ 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: thomas.powles1@nhs.net.
² Bradford Hill Clinical Research Center, Santiago, Chile.
³ Gustave Roussy, Villejuif, France.
⁴ Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
⁵ Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
⁶ MD Anderson Cancer Center, Houston, USA.
⁷ Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
⁸ Department of Internal Medicine, University of Pavia, Pavia, Italy.
⁹ Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Latin American Cooperative Oncology Group, Porto Alegre, Brazil.
¹⁰ Fundación Richardet Longo, Instituto Oncológico de Córdoba, Córdoba, Argentina.
¹¹ Westmead Hospital and Macquarie University, Westmead and Sydney, Australia.
¹² Division of Medical Oncology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, USA.
¹³ Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
¹⁴ Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany.
¹⁵ Roswell Park Comprehensive Cancer Center, Buffalo.
¹⁶ Exelixis, Inc., Alameda.
¹⁷ Bristol Myers Squibb, Princeton.
¹⁸ Memorial Sloan Kettering Cancer Center, New York.
¹⁹ Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston; Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

Abstract

Background: 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 and methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov, NCT03141177.

Keywords: IMDC; cabozantinib; immunotherapy; nivolumab; phase III; renal cell carcinoma.

Associated data

ClinicalTrials.gov/NCT03141177