CheckMate-274 Trial

Design - Phase 3 adjuvant nivolumab vs placebo, high-risk muscle-invasive urothelial carcinoma after radical resection (CheckMate-274, NCT02632409); primary endpoint DFS (ITT + PD-L1 >=1%).

DFS (primary) - ITT median 20.8 vs 10.8 mo, HR 0.70 (98.22% CI 0.55-0.90), P<0.001 (NEJM 2021); PD-L1 >=1% subgroup HR 0.53. 5-yr update (Annals 2026): 21.9 vs 11.0 mo, HR 0.74.

OS (5-yr follow-up) - First OS data (Annals of Oncology, Jan 2026): median 75.0 vs 50.1 mo, HR 0.83 (95% CI 0.67-1.02) - 95% CI crosses unity, not formally significant.

Safety - Consistent with the established nivolumab profile; common AEs rash, fatigue, diarrhea, pruritus, musculoskeletal pain, urinary tract infection.

Regulatory - FDA approved August 19, 2021 - adjuvant nivolumab for high-risk urothelial carcinoma after radical resection.

Sponsor / drug - Bristol Myers Squibb + Ono Pharmaceutical; nivolumab (Opdivo).

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.

Disease-Free Survival (DFS) — Primary Endpoint

ITT population (primary analysis, NEJM 2021): median DFS 20.8 mo with nivolumab vs. 10.8 mo with placebo (HR 0.7, 98.22% CI 0.55-0.90, P<0.001). PD-L1 ≥1% subgroup: HR 0.53 (NEJM 2021 primary). 5-year update (Annals of Oncology 2026): median DFS 21.9 vs. 11.0 mo, HR 0.74 (95% CI 0.61-0.90).

Overall Survival (OS)

First overall survival data from the 5-year follow-up (Galsky/Bajorin, Annals of Oncology, January 2026): median OS 75.0 months with nivolumab (95% CI 56.7-NE) vs. 50.1 months with placebo (38.0-72.1); HR 0.83 (95% CI 0.67-1.02). The 95% CI crosses unity — OS improvement is clinically meaningful (nearly 25 months absolute difference in medians) but did not reach conventional statistical significance in the hierarchical testing framework. DFS benefit remained durable alongside this OS signal.

Safety & Tolerability

Adverse events significant but manageable; consistent with the established nivolumab safety profile. Most common AEs: rash, fatigue, diarrhea, pruritus, musculoskeletal pain, urinary tract infection.

Clinical Implications

✅ Established adjuvant SOC for high-risk MIUC. Established adjuvant nivolumab as SOC for high-risk MIUC post-radical surgery. With NIAGARA now showing OS benefit with perioperative durvalumab in cisplatin-eligible MIBC, field is shifting to perioperative approach; CheckMate-274 remains relevant for cisplatin-ineligible patients, upper tract disease, or when neoadjuvant was declined/not feasible.

What is the CheckMate-274 trial? (Note on this page's slug)

CheckMate-274 is a Phase 3 randomized, double-blind trial (NCT02632409) of adjuvant nivolumab (Opdivo) versus placebo in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery. Disease-free survival in the overall (intent-to-treat) population and in the PD-L1 >=1% subgroup was the primary endpoint. This page's URL slug reads 'checkmate-274,' but its content and data describe CheckMate-274.

What did CheckMate-274 show for disease-free survival?

Adjuvant nivolumab significantly prolonged disease-free survival. In the primary analysis (NEJM 2021), median DFS was 20.8 versus 10.8 months in the intent-to-treat population (HR 0.70; 98.22% CI 0.55-0.90; P<0.001), with a greater disease-free survival benefit in the PD-L1 >=1% subgroup (HR 0.53). The 5-year update (Annals of Oncology 2026) confirmed durable benefit with median DFS 21.9 versus 11.0 months (HR 0.74).

Is adjuvant nivolumab FDA approved for bladder cancer?

Yes. On August 19, 2021 the FDA approved nivolumab (Opdivo) for the adjuvant treatment of adults with urothelial carcinoma who are at high risk of recurrence after radical resection, based on the CheckMate-274 disease-free survival benefit. It established adjuvant immunotherapy as a standard of care in this setting.

What did the long-term overall survival data show?

The first overall survival results, from the 5-year follow-up (Galsky/Bajorin, Annals of Oncology, January 2026), showed median OS of 75.0 months with nivolumab versus 50.1 months with placebo (HR 0.83; 95% CI 0.67-1.02). Because the 95% confidence interval crosses unity, the overall survival improvement is a favorable trend but was not formally statistically significant.

How does CheckMate-274 fit with perioperative durvalumab (NIAGARA)?

CheckMate-274 established adjuvant nivolumab as a standard of care for high-risk muscle-invasive urothelial carcinoma after radical surgery. With NIAGARA now showing an overall survival benefit for perioperative (neoadjuvant plus adjuvant) durvalumab in cisplatin-eligible muscle-invasive bladder cancer, the field is increasingly shifting toward perioperative strategies, while adjuvant nivolumab remains an option, particularly for patients who did not receive neoadjuvant immunotherapy.