CheckMate 274 follow up data boost nivolumab potential for high-risk bladder cancer

In the extended follow up of the phase III CheckMate 274 trial, nivolumab continued to show benefit for patients with muscle-invasive urothelial carcinoma (MIUC; bladder, ureter, or renal pelvis) who were at high risk for recurrence following bladder resection.

Adjuvant nivolumab became the standard of care (SoC) for this subgroup of patients based on the initial Checkmate 274 findings. “The initial results were reported after a minimum follow up of 5.9 months,” said Dr Matthew Galsky from the Icahn School of Medicine at Mount Sinai, New York, New York, US, at ASCO GU 2023.

“[We initially reported that] adjuvant nivolumab improved disease-free survival (DFS) in the intention-to-treat (ITT) population and in patients with tumour PD-L1 ≥1 percent,” Galsky continued.

In the current analysis, the DFS benefit with nivolumab was still seen after a minimum follow up of 31.6 months. Compared with the placebo arm, median DFS in the nivolumab arm was twice as long in the ITT cohort (22.0 vs 10.9 months; hazard ratio [HR], 0.71) and nearly seven times longer in the PD-L1 ≥1 subgroup (52.6 vs 8.4 months; HR, 0.52). [ASCO GU 2023, abstract LBA443]

“DFS also favoured adjuvant nivolumab vs placebo across multiple prespecified subgroups based on age, sex, region, and performance status … and those defined by tumour characteristics including the presence of minor histologic variants, pathologic lymph node status, and pathological T stage,” said Galsky.

Other survival endpoints

The current findings also demonstrated the benefit of nivolumab in terms of the secondary endpoint of nonurothelial tract recurrence-free survival (NUTRFS). Median NUTRFS was markedly longer with nivolumab vs placebo (25.9 vs 13.7 months [ITT] and 52.6 vs 8.4 months [PD-L1 ≥1 percent]). The respective HRs for these groups were 0.72 and 0.53.

A similar trend was seen in terms of the exploratory endpoint of distant metastasis-free survival (DMFS). DMFS favoured nivolumab over placebo in both the ITT population (median 47.1 vs 28.7 months; HR, 0.74) and the PD-L1 subgroup (median not reached vs 20.7 months; HR, 0.58).

Nivolumab also trumped placebo in terms of secondary progression-free survival, another exploratory endpoint (HRs, 0.79 and 0.54 for the ITT cohort and PD-L1 subgroup, respectively).

Sustained effects over time

The study randomized 709 participants (mean age 65.6 years) 1:1 to IV nivolumab 240 mg Q2W or placebo for up to a year. Of these, 40 percent had PD-L1 expression ≥1 percent. About 80 percent of participants had urinary bladder tumours at initial diagnosis.

From the initial follow up of about 6 months to the current analysis with a minimum follow up of nearly 3 years, the effect of adjuvant nivolumab across primary, secondary, and exploratory endpoints were remarkably stable over time, Galsky noted. The HRs for DFS, NUTRFS, and DMFS in the PD-L1 subgroup continued to improve compared with the primary analysis results.

“It is important to point out that [these occurred] with a fixed duration of treatment. Adjuvant treatment was limited to 1 year, yet the effects were sustained over time,” Galsky stressed.

Safety-wise, no new signals were identified. Despite the higher incidence of grade 3/4 treatment-related adverse events with nivolumab vs placebo (18 percent vs 7 percent), these rates were consistent with those observed in the primary analysis.

“[The current] results further support adjuvant nivolumab as SoC for patients with MIUC at high risk for recurrence after radical surgery,” he concluded.