April 16, 2018—Today, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (a PD-1 inhibitor) and ipilimumab (a CTLA-4 inhibitor) for the frontline treatment of intermediate- and poor-risk patients with advanced renal cell carcinoma (RCC).
 
This approval is based on results from the phase III CheckMate 214 trial (NCT02231749) in which 847 intermediate- or poor-risk patients with previously untreated advanced or metastatic RCC were randomized to receive the dual immunotherapy combination (n=425) or sunitinib (n=422). The objective response rate (ORR) for patients receiving the combination was 41.6% compared with 26.5% for patients receiving the tyrosine kinase inhibitor. The median overall survival (OS) for patients receiving sunitinib was 25.9 months, and was not yet estimable for patients receiving the immunotherapy combination. Overall, the use of nivolumab and ipilimumab reduced the risk of death by 32% compared with the use of sunitinib (HR 0.63; 95% CI, 0.44-0.89; P<0.0001). The efficacy of this combination was not evaluated in patients with favorable-risk disease.
 
Nivolumab was previously approved in metastatic RCC and several other cancer types. Ipilimumab was previously granted accelerated approval in combination with nivolumab for patients with unresectable or metastatic melanoma.
 
Adverse events (AEs) leading to treatment discontinuation occurred in 22% of patients in the nivolumab/ipilimumab group compared with 12% in the sunitinib group. The most common grade 3/4 AEs in the combination group were fatigue (4%) and diarrhea (4%). Other AEs included rash, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite.
 
Updated prescribing information for nivolumab can be found here. Updated prescribing information for ipilimumab can be found here.
 
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Jonathan A. Bell
Published Online: Monday, April 16, 2018