Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
Bristol-Myers Squibb
Enrollment:
709
Study Design:
This was an international, randomized, double-blind phase III trial. The original study randomized patients between IV nivolumab (NIVO) Q 2 weeks and IV placebo (PBO) Q 2 weeks after surgery. Patients were high-risk MIUC; if ypT2-ypT4a or ypN+, received neoadjuvant cisplatin CT; if pT3-pT4a or pN+, or did not receive neoadjuvant cisplatin CT and were ineligible for or refused adjuvant cisplatin CT. Patients underwent radical surgery within 120 days and were disease free within 4 weeks of study dosing.
Rationale:
Based on the previous Checkmate 274 trial, adjuvant nivolumab for 1 year has become the standard of therapy after radical surgery for patients with muscle invasive urothelial cancer (MIUC) due to improvement in disease-free survival. This presentation at the AUA 2023 was on the extended follow-up of the muscle invasive bladder cancer cohort (MIBC) with a median follow-up of 3 years.
Endpoints:
The primary endpoint was disease-free survival (DFS) in the ITT population and DFS in all randomized patients with PD-L1 ≥ 1%.The secondary endpoints were distant metastasis-free survival and non-urothelial tract recurrence-free survival (RFS).
Comments:
Only approximately 40% of patients in this study received prior neoadjuvant chemotherapy. From the original presentation, it appeared that the HRs overlapped 1 for patients with upper tract tumors and more benefit was seen in the cohort with MIBC. With extended 3-year median follow-up, continued improvement in DFS was maintained. Although, overall survival data have still not been presented, this study is practice changing.
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. HR favored NIVO vs PBO for non-urothelial tract recurrence-free survival (HR 0.64) and distant metastasis-free survival (HR 0.70). Grade 3–4 treatment-related adverse events occurred in 17.3% and 5.8% of NIVO and PBO pts, respectively. In this study, there was a continued benefit in DFS, distant-metastasis-free survival, and RFS in both the ITT and muscle-invasive bladder cancer populations. Of note, all patients with PD-L1 greater than or equal to 1%, experienced a benefit in DFS. However, even MIBC with PD-L1 less than 1% still saw a benefit in DFS with nivolumab.
