Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial.

BACKGROUND

Nivolumab plus cabozantinib (NIVO+CABO) showed significant benefits over sunitinib (SUN) in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for previously untreated advanced renal cell carcinoma (RCC) in the phase III CheckMate 9ER trial (NCT03141177). We report final, updated efficacy and safety results with median follow-up of 5.6 years.

PATIENTS AND

METHODS

Patients with advanced RCC were randomized to first-line NIVO 240 mg intravenously every 2 weeks plus CABO 40 mg p.o. o.d. or SUN 50 mg p.o. o.d. (4 weeks each 6-week cycle) until disease progression or unacceptable toxicity (maximum 2 years of NIVO). The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety.

RESULTS

Median (range) follow-up was 5.6 years [67.6 (60.2-80.2) months]. In intent-to-treat patients (NIVO+CABO, n = 323; SUN, n = 328), PFS favored NIVO+CABO versus SUN [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.49-0.70]. Median PFS was 16.4 versus 8.3 months, respectively; 60-month PFS rates were 13.6% versus 3.6%. OS favored NIVO+CABO versus SUN (HR 0.79, 95% CI 0.65-0.96). Median OS was 46.5 versus 35.5 months, respectively; 60-month OS rates were 40.9% versus 35.4%. ORR was greater with NIVO+CABO versus SUN (55.7% versus 27.4%; complete response 13.9% versus 4.6%). The probability of remaining in response through 60 months with NIVO+CABO versus SUN was 22.0% versus 10.0%. In all treated patients (n = 320 each arm), any-grade (grade 3-4) treatment-related adverse events occurred in 97.5% (67.8%) versus 93.1% (55.0%) with NIVO+CABO versus SUN, respectively. No new deaths due to study drug toxicity occurred since the 32.9-month median follow-up.

CONCLUSIONS

Long-term efficacy benefit was observed with NIVO+CABO over SUN in this final follow-up from CheckMate 9ER and safety was consistent with previous reports. These results reaffirm NIVO+CABO as a standard of care for previously untreated advanced RCC.