Motzer RJ, et al. - Experts sought to compare the efficacy of nivolumab plusipilimumab with sunitinib for the treatment of previously untreated clear-cell advanced renal-cell carcinoma in adult patients. Substantially higher overall survival and objective response rates were gained via nivolumab plus ipilimumab compared to sunitinib in the case of intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma.

Methods

• Adults were randomly allocated in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle).
• Overall survival (alpha level,0.04), objective response rate (alpha level,0.001), and progression-free survival (alpha level,0.009) among patients with intermediate or poor prognostic risk served as the coprimary endpoints.

Results

• Researchers allocated 1,096 patients to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk.
• The 18-month overall survival rate was found to be 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib at a median follow-up of 25.2 months in intermediate- and poor-risk patients.
• It was noted that the median overall survival was not reached with nivolumab plus ipilimumab vs 26.0 months with sunitinib (hazard ratio for death, 0.63; P < 0.001).
• Data illustrated that the objective response rate was 42% vs 27% (P < 0.001), and the complete response rate was 9% vs 1%.
• It was disclosed that the median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P=0.03, not significant per the prespecified 0.009 threshold).
• The occurrence of treatment-related adverse events was noted in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group.
• Furthermore, the presence of grade 3 or 4 events was discovered in 250 patients (46%) and 335 patients (63%), respectively.
• In 22% and 12% of the patients in the respective groups, treatment-related adverse events were noted which led to discontinuation.