Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
Bristol-Myers Squibb
Enrollment:
709
Study Design:
CheckMate 274 is a phase 3, randomized, double-blind, multicenter study of adjuvant nivolumab versus placebo in patients with high-risk MIUC. Inclusion criteria were: Patients with ypT2-ypT4a or ypN+ MIUC who had neoadjuvant cisplatin-based CT, or pT3-pT4a or pN+ MIUC without prior neoadjuvant cisplatin-based CT, and not eligible for or refused adjuvant cisplatin-based CT; radical surgery performed within the past 120 days and disease-free status within 4 weeks of dosing. Patients were randomized 1:1 to nivolumb IV 240 mg every 2 weeks vs. placebo IV every 2 weeks x 1 year. Stratification factors included: PD-L1 status (<1% vs ≥ 1%) , prior neoadjuvant cisplatin-based chemotherapy and nodal status.
Rationale:
Radical surgical resection is the standard of care for patients with MIUC. Adjuvant therapy after radical surgery is not currently recommended for patients who have received neoadjuvant therapy... For patients who have not had neoadjuvant cisplatin-based CT, adjuvant cisplatin-based CT may be offered but the level of evidence is low. Nivolumab, a PD-1 immune checkpoint inhibitor, is approved as monotherapy for treatment of platinum-resistant metastatic UC. Until this trial , no immunotherapy has shown efficacy as adjuvant therapy in patients with MIUC at high risk for recurrence after radical surgery.
Endpoints:
The primary endpoints were disease free survival in the intent to treat (ITT) population and DFS in all randomized patients with tumor PD-L1 ≥ 1%.
Comments:
Nivolumab is the first systemic immunotherapy to demonstrate a statistically significant and clinically meaningful improvement in outcomes when administered as adjuvant therapy to patients with MIUC. The FDA has granted priority review, although the overall survival data are not yet mature. These results may well support nivolumab monotherapy as a new standard of care in the adjuvant setting for patients with high-risk MIUC after radical surgery, irrespective of PD-L1 status and prior neoadjuvant chemotherapy. The results differ from what was found in the adjuvant atezolizumab trial highlighted below.
Results:
Adjuvant nivolumab significantly improved DFS in patients with high-risk MIUC after radical surgery, both in the ITT and PD-L1 ≥ 1% populations. In the ITT population, the median DFS with nivolumab was 21.0 (17.1–33.4) months vs 10.9 (8.3–13.9) months, HR, 0.70 (98.31% CI, 0.54–0.89) in patients treated with placebo (p < 0.001). In the PD-L1 ≥ 1% population, median DFS was NR (22.0–NE) vs 10.8 (5.7–21.2) months, HR, 0.53 (98.87% CI, 0.34–0.84), respectively (p < 0.001). No deterioration in health related quality of life, as measured by change in EORTC QLQ-C30 global health status score, was observed with nivolumab vs placebo.
