Introduction:

The phase 3 CheckMate 274 trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical surgery met the primary endpoints of improvement in disease-free survival (DFS) with NIVO vs PBO in intent-to-treat (ITT) patients and in patients with tumor programmed death ligand 1 (PD-L1) expression ≥1%; efficacy improvements were continued at the 3-year follow-up. Interim overall survival (OS) favored NIVO vs PBO. Efficacy benefits were also seen in patients with muscle-invasive bladder cancer (MIBC). Here, we report extended 5-year follow-up results, including exploratory MIBC and circulating tumor (ct)DNA data.

Methods:

Patients were randomized 1:1 to NIVO 240 mg IV every 2 weeks or PBO for ≤1 year of adjuvant treatment. Patients had radical surgery ± neoadjuvant chemotherapy (NAC) and were at high risk of recurrence. Primary endpoints were DFS in ITT patients and patients with PD-L1 ≥1%. OS and disease-specific survival (DSS) were secondary endpoints. Analyses of the MIBC subgroup and of ctDNA (with the Natera Signatera assay) were exploratory.

Results:

In total, 709 patients (NIVO, n=353; PBO, n=356) were randomized. At 43.4 months median follow-up, improvement in DFS was observed with NIVO vs PBO in ITT and PD-L1 ≥1% patients; OS and DSS were also longer with NIVO vs PBO in these patient populations (Table). Among patients with MIBC (NIVO, n=279; PBO, n=281), DFS was improved with NIVO vs PBO in all patients, those with PD-L1 ≥1%, with prior NAC, and without prior NAC (Table). OS and DSS also favored NIVO vs PBO in patients with MIBC (Table). No new safety signals were reported. Evaluable cycle 1/day 1 ctDNA results were available for 133/709 patients (18.8%); 54/133 (40.6%) patients had detectable baseline ctDNA. Improvement in DFS was observed with adjuvant NIVO vs PBO in patients with cycle 1/day 1 detectable ctDNA, but not in patients with undetectable ctDNA at cycle 1/day 1 in this small data set.

Conclusion:

At 5 years of follow-up, continued improvement in DFS with NIVO vs PBO was observed. OS and DSS were longer with NIVO vs PBO. Efficacy benefit was seen both in ITT patients and in patients with PD-L1 ≥1%. In addition, continued improvement in DFS, and longer OS and DSS were observed with NIVO vs PBO in patients with MIBC. In exploratory analyses, ctDNA status at cycle 1/day 1 of NIVO was correlated with improvement in DFS. This finding was consistent with prior observations of adjuvant immune checkpoint inhibitor blockade in MIUC. These long-term results support adjuvant NIVO as a standard of care in patients with high-risk MIUC including those with MIBC regardless of prior NAC.

Funding: Bristol Myers Squibb