Adjuvant nivolumab appears to improve survival outcomes in patients with muscle-invasive bladder cancer (MIBC) who have undergone radical surgery, regardless of prior exposure to neoadjuvant chemotherapy (NAC), according to additional data from the phase III CheckMate 274 trial.

Over a median follow-up of 34.5 months, disease-free survival (DFS) was consistently longer with nivolumab than with placebo in subgroups of patients with prior NAC (median, 19.6 vs 8.3 months; hazard ratio [HR], 0.58, 95 percent confidence interval [CI], 0.43?0.79) and those without prior NAC (median, 25.9 vs 13.7 months; HR, 0.69, 95 percent CI, 0.50?0.94), reported Dr Matthew Milowsky from the University of North Carolina School of Medicine in Chapel Hill, North Carolina, US. [ASCO GU 2025, abstract 658]

The 3-year DFS rates were 46.5 percent with nivolumab vs 28.9 percent with placebo among patients with prior NAC and 46.9 percent vs 35.4 percent, respectively, among those without prior NAC, Milowsky added.

Results for overall survival (OS) also favoured nivolumab in the entire MIBC cohort (median, not reached vs 39.9 months; HR, 0.70, 95 percent CI, 0.55?0.90) and in subgroups of patients with PD-L1 ≥1% (median, not reached vs 37.6 months; HR, 0.48, 95 percent CI, 0.29?0.77), those with prior NAC (median, 55.2 vs 40.2 months; HR, 0.74, 95 percent CI, 0.53?1.03), and those without prior NAC (median, not reached vs 37.7 months; HR, 0.67, 95 percent CI, 0.47?0.95).

The respective OS rates with nivolumab vs placebo at 3 years were 64.2 percent vs 53.7 percent in the MIBC cohort, 71.8 percent vs 52.0 percent in the PD-L1 ≥1% subgroup, 64.5 percent vs 53.4 percent in the prior NAC subgroup, and 63.8 percent vs 53.9 percent in the no-prior NAC subgroup.

“Safety in patients with MIBC was consistent with previous data in intention-to-treat population, and no new safety signals were identified,” Milowsky noted.

Treatment-related adverse events (TRAEs) occurred in 80 percent of patients on nivolumab and in 56 percent of those on placebo, including grade ≥3 TRAEs in 17 percent and 6 percent, respectively. TRAEs led to discontinuation in 15 percent and 2 percent of patients, respectively.

Frequently reported TRAEs included pruritus (23 percent vs 11 percent), fatigue (18 percent vs 12 percent), and diarrhoea (18 percent vs 12 percent). The most common grade ≥3 TRAEs were elevations in lipase (5 percent vs 2 percent) and amylase (4 percent vs 1 percent) concentrations.

Targeting treatment

“Adjuvant nivolumab for high-risk MIBC demonstrates significant overall survival and event-free survival benefit and is the standard of care in this space,” according to study discussant Dr Elizabeth Plimack from the Fox Chase Cancer Center Philadelphia, Pennsylvania, US.

The benefit observed in CheckMate 274 compares favourably to that provided by adjuvant regimens that are now standard of care across multiple tumour types, Plimack added.

She stressed the need for targeted treatment and pointed to the potential of biomarkers to aid in the identification of patients who need adjuvant immunotherapy and, among who need it, who is likely to benefit in order to avoid overtreatment.

CheckMate 274 included 709 patients with high-risk muscle-invasive urothelial carcinoma. These patients were randomly assigned to receive adjuvant treatment with nivolumab 240 mg every 2 weeks (n=353, mean age 65.3 years, 75 percent male) or placebo (n=356, mean age 65.9 years, 77 percent male) for up to 1 year. These patients were enrolled within 120 days of undergoing radical surgery, with 12.3 percent having received neoadjuvant cisplatin.

The current analysis included 560 patients with MIBC, including 279 treated with nivolumab and 281 with placebo. Baseline characteristics were consistent with the intention-to-treat muscle-invasive urothelial carcinoma population.