On August 19, 2021, the FDA accelerated the approval of nivolumab (Opdivo; Bristol Myers Squibb) for the adjuvant treatment of patients with urothelial carcinoma who are at high risk for recurrence after undergoing radical resection. This is the first FDA approval of any immunotherapy for adjuvant treatment of patients with high-risk urothelial carcinoma.
This approval also converted the accelerated approval of nivolumab for advanced or metastatic urothelial carcinoma to a regular approval. Nivolumab has previously been approved for many indications.
This new approval was based on the CheckMate 274 study, a randomized, double-blind, placebo-controlled clinical trial of patients who were within 120 days of radical resection of urothelial carcinoma of the bladder or upper urinary tract and were at high risk for recurrence. Patients were randomized in a 1:1 ratio to nivolumab 240 mg or to placebo every 2 weeks until recurrence or unacceptable toxicity, for a maximum of 1 year.
The primary end point was disease-free survival (DFS) in the ITT population and in patients with PD-L1 expression ≥1%. A prespecified interim analysis showed a significant improvement in DFS in the nivolumab arm versus placebo. In the ITT analysis, the median DFS was 20.8 months with nivolumab versus 10.8 months with placebo (P = .0008). For patients with PD-L1 ≥1%, the median DFS was not reached in the nivolumab arm versus 8.4 months in the placebo arm (P = .0005). The overall survival (OS) data are immature, with 33% of deaths reported in the overall study population.
The most common (≥20%) adverse events with nivolumab in the CheckMate 274 study were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and urinary tract infection.