Introduction: Despite radical resection, patients with muscle-invasive urothelial carcinoma (MIUC) remain at high risk for lethal metastatic recurrence, mostly within 2–3 years of surgery. CheckMate 274 is a phase 3, randomized, double-blind trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in high-risk MIUC after radical resection. The 2 primary endpoints (disease-free survival [DFS] in intent-to-treat [ITT] patients [pts] and in pts with tumor programmed death ligand 1 [PD-L1] expression = 1%) were met. At minimum follow-up of 11.0 months (median: 23.3 months), DFS benefit with NIVO vs PBO was observed in ITT pts (HR 0.70; 95% CI 0.57–0.85) and in pts with PD-L1 = 1% (HR 0.53; 95% CI 0.38–0.75); efficacy benefits (DFS [HR 0.61; 95% CI 0.49–0.77], non-urothelial tract recurrence-free survival [NUTRFS], and distant metastasis-free survival [DMFS]) were also seen in pts with muscle invasive bladder cancer (MIBC). We report extended follow-up results for pts with MIBC (minimum: 31.6 months [median: 36.1 months] in the ITT population). Methods: Pts were randomized 1:1 to NIVO 240 mg IV Q2W or PBO for = 1 year of adjuvant treatment and stratified by nodal status, prior neoadjuvant cisplatin, and tumor PD-L1 expression. Pts had radical resection ± neoadjuvant chemotherapy and were at high risk of recurrence. Primary endpoints are DFS in ITT pts and in pts with PD-L1 = 1%. NUTRFS is a secondary endpoint. DMFS and safety are exploratory endpoints. Analysis of the MIBC subgroup is exploratory. Results: Of 709 randomized pts, 560 had MIBC (NIVO, n = 279; PBO, n = 281). DFS was improved with NIVO vs PBO in all pts with MIBC (HR 0.63), and in the PD-L1 = 1% (HR 0.44) and PD-L1 < 1% (HR 0.74) subgroups (Table). HR favored NIVO vs PBO for NUTRFS (HR 0.64) and DMFS (HR 0.70) (Table). Grade 3–4 treatment-related adverse events occurred in 17.3% and 5.8% of NIVO and PBO arm pts, respectively. Conclusions: With extended 3-year median follow-up, continued improvement in DFS, NUTRFS, and DMFS were observed with NIVO vs PBO in pts with MIBC. DFS benefit was evident regardless of tumor PD-L1 expression. Safety was consistent with previous data in the ITT population with no new safety signals identified. These results further support NIVO as a standard of care for high-risk MIBC after radical resection. SOURCE OF Funding: Bristol Myers Squibb
