Nivolumab (Opdivo) has been shown to have antitumor activity in patients with metastatic urothelial carcinoma who received platinum treatment. However, the role of this agent as adjuvant therapy in high-risk muscle-invasive urothelial carcinoma following surgery has been unclear. In a recent study, researchers evaluated the efficacy and safety of adjuvant nivolumab compared with placebo in patients with muscle-invasive urothelial carcinoma following radical surgery (Bajorin DF, et al. N Engl J Med. 2021;384:2102-2104).
In the phase 3 CheckMate 274 study, patients with muscle-invasive urothelial carcinoma who had undergone radical surgery were randomized in a 1:1 ratio to nivolumab 240 mg intravenously (N = 353) or placebo (N = 356) every 2 weeks for up to 1 year.
In the nivolumab arm, the tumor of origin was urinary bladder carcinoma in 79% of patients and upper tract disease in 21% of patients. In the placebo arm, the tumor of origin was urinary bladder in 78.9% of patients and upper tract disease in 21.1% of patients. Approximately 40% of patients in both arms were PD-L1 positive and about 43% had received prior cisplatin-based neoadjuvant chemotherapy.
The primary end point of the trial was disease-free survival (DFS) among the intention-to-treat (ITT) population and among patients with a PD-L1 expression level of ≥1%. A secondary end point was survival free from recurrence outside the urothelial tract.
The researchers reported that DFS was significantly longer in the nivolumab arm versus the placebo arm, both in the ITT population and among patients with a PD-L1 expression level of ≥1%. At a median follow-up of 20.9 months in the nivolumab arm and 19.5 months in the placebo arm in the ITT population, the median DFS was 20.8 months and 10.8 months, respectively. The 6-month DFS rates were 74.9% versus 60.3%, respectively. Among patients with a PD-L1 expression level of ≥1%, the 6-month DFS rate was 74.5% with nivolumab and 55.7% with placebo.
The median survival free from recurrence outside the urothelial tract in the ITT population was 22.9 months with nivolumab and 13.7 months with placebo.
The 6-month survival free from recurrence outside the urothelial tract in patients with a PD-L1 expression level of ≥1% was 75.3% with nivolumab and 56.7% with placebo.
The safety profile of nivolumab was consistent with previously reported studies in patients with solid tumors. Grade 3 or higher treatment-related adverse events occurred in 17.9% of patients in the nivolumab arm and 7.2% of patients in the placebo arm. Any-grade treatment-related adverse events leading to discontinuation occurred in 12.8% in the nivolumab arm and 2% of patients in the placebo arm. The most common treatment-related adverse events in the nivolumab arm were pruritus, fatigue, diarrhea, and rash.
“The CheckMate 274 trial showed a significant and clinically meaningful benefit of adjuvant systemic immunotherapy as compared with placebo, both in the intention-to-treat population and in patients with a PD-L1 expression level of 1% or more,” concluded the researchers.