Renal cell carcinomas (RCCs) arise from the renal cortex; many patients with RCC are asymptomatic until the disease is either locally advanced and unresectable, or metastatic. To date, nivolumab (Opdivo®), a human immunoglobulin G4 (Ig4) monoclonal antibody directed against programmed death-1 (PD-1), has not been approved throughout Europe for the treatment of patients with advanced RCC who did not receive prior treatment. Since April 2018, nivolumab in combination with ipilimumab has been approved in the US for the initial treatment of patients with intermediate- or poor-risk advanced RCC.

The CheckMate 214 trial assessed the combination of nivolumab plus ipilimumab versus sunitinib monotherapy in patients with previously untreated advanced RCC in 1,096 patients, whereat 79% of the overall study population had intermediate- or poor-risk RCC. Analyses showed that intermediate- and poor-risk patients who received nivolumab plus ipilimumab showed a statistically significant benefit in overall survival (OS) and in the objective response rate (ORR) as compared with sunitinib. Thus, the 12-month OS rate was 80% versus 72%, the 18-month OS rate was 75% versus 60%, with a hazard ratio (HR) for death of 0.63 (99.8% CI, 0.44–0.89; p <0.001) and ORR of 42% versus 27% (p <0.001) in the respective treatment groups. Health-related quality of life (HRQoL) analyses showed better results in intermediate- and poor-risk patients treated with nivolumab plus ipilimumab. Median progression-free survival (PFS) was prolonged with nivolumab plus ipilimumab, although the difference was not statistically significant. Treatment-related AEs of grade 3 or 4 occurred in 46% (nivolumab-plus-ipilimumab group) and 63% (sunitinib group) of patients. The number of treatment-related deaths was higher in patients receiving nivolumab plus ipilimumab.

CheckMate 214 study results show that the combination of nivolumab and ipilimumab provides a clinical benefit in previously untreated, intermediate- and poor-risk patients. However, the high rate of treatment-related adverse effects (AEs) needs to be taken into consideration. Moreover, data regarding AEs for intermediate- and poor-risk patients and, additionally, long-term efficacy and safety data of the combination therapy would be of interest. Since CheckMate 214 is the only phase III trial providing results of nivolumab plus ipilimumab in untreated patients with advanced RCC, more data is needed to evaluate this combination regimen as a first-line therapy.