Some patients are not eligible for cisplatin due to factors such as reduced kidney function. Adjuvant nivolumab, in turn, may represent a treatment option for these individuals, in order to reduce the risk of recurrence or death
During the 2021 Genitourinary Cancers Symposium, CheckMate 274 (NCT02632409) was presented, a randomized, open-label, double-blind, multicenter, phase III trial that evaluated the use of adjuvant nivolumab in patients undergoing radical surgery for high-risk muscle-invasive urothelial carcinoma of the bladder, ureter, or renal pelvis.
The trial involved 709 patients with muscle-invasive urothelial carcinoma who underwent radical surgery with or without neoadjuvant cisplatin-based chemotherapy. There was a high risk of recurrence, based on the stage of the tumor. Patients were randomly assigned in the 1:1 ratio to receive nivolumab 240 mg every two weeks, or placebo, for up to one year of adjuvant treatment.
The primary endpoint involved disease-free survival (DFS) in all randomized participants (population intended to treat – ITT) and in those with tumor expression of PD-L1 ≥ 1%. DFS was stratified by nodal status, previous neoadjuvant cisplatin and PD-L1 expression. The secondary endpoint included recurrence-free survival outside the urothelial tract, in ITT patients and in PD-L subjects ≥ 1%. Safety, in turn, was an exploratory outcome.
The median DFS was significantly higher for patients receiving postoperative treatment with nivolumab compared to those in the placebo group (21 versus 10.9 months; HR 0.70; CI 98.31%: 0.54–0.89; P = 0.0006), as well as demonstrated superiority in the PD-L1-positive population (median not reached versus 10.8 months; HR 0.53; CI 98.87%: 0.34–0.84; P = 0.0004).
DFS and recurrence-free survival outside the urothelial tract were better with nivolumab versus placebo, both in the ITT patient group (24.6 versus 13.7 months; HR 0.72; 95% CI: 0.58-0.89) as well as in the PD-L1-positive population (median not reached versus 10.9 months; HR 0.54; 95% CI: 0.38-0.77). The increase in DFS with nivolumab was generally consistent in all subgroups.
The serious adverse events related to treatment (grade 3-4) were more observed among patients receiving nivolumab (17.9%) than in the placebo group (7.2%). The most common events of grade 3 or higher were diarrhea, colitis, and pneumonitis in patients in the immunotherapy arm; and colitis, diarrhea, increased gamma-glutamyl transferase and hepatitis in patients in the placebo arm.
Therefore, nivolumab demonstrated a statistically and clinically significant improvement in DFS versus placebo in patients with high-risk muscle-invasive urothelial carcinoma, after radical surgery, both in the ITT population and in the PD-L1 ≥ 1%. Adverse events were manageable and consistent with previous reports. The authors conclude that these results support the use of adjuvant nivolumab as a potential new standard of treatment for this evaluated population.