Extended follow-up results from the CheckMate 274 trial.
Matt D. Galsky, Alfred Alfred Witjes, Jürgen E. Gschwend, Michael Schenker, Begoña P. Valderrama, Yoshihiko Tomita, Aristotelis Bamias, Thierry Lebrét, Shahrokh F. Shariat, Se Hoon Park, Mads Agerbæk, Gautam Jha, Frank Stenner, Santanu Dutta, Federico Nasroulah, Joshua Zhang, Lynne Brophy, Dean F. Bajorin
Abstract
LBA443 Background: The 2 primary endpoints of the CheckMate 274 trial were met as nivolumab (NIVO) improved disease-free survival (DFS) versus placebo (PBO) in the intent-to-treat (ITT) population and in patients with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. We report extended follow-up data. Methods: CheckMate 274 is a phase 3, double-blind trial of adjuvant NIVO versus PBO for high-risk muscle-invasive urothelial carcinoma (MIUC) (bladder, ureter, or renal pelvis) after radical resection. Patients were randomly assigned 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 year of treatment. Patients had pathologic evidence of UC at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1. Primary endpoints were DFS in ITT patients and in patients with PD-L1 ≥ 1%. DFS was also analyzed in prespecified subgroups. Overall survival and non–urothelial tract recurrence-free survival (NUTRFS) in ITT patients and in patients with PD-L1 ≥ 1% were secondary endpoints. Distant metastasis-free survival (DMFS) and safety were exploratory endpoints. Results: There were 353 patients randomly assigned to NIVO (PD-L1 ≥ 1%, n = 140) and 356 to PBO (PD-L1 ≥ 1%, n = 142). With median follow-up of 36.1 months (minimum follow-up, 31.6 months), median DFS was 22.0 months with NIVO versus 10.9 months with PBO in ITT patients and 52.6 months with NIVO versus 8.4 months with PBO in patients with PD-L1 ≥ 1% (Table). DFS benefit was seen in most subgroups analyzed including age, sex, ECOG PS, nodal status, prior cisplatin-based chemotherapy, and PD-L1 status. NUTRFS and DMFS benefits with NIVO versus PBO were also observed in both populations (Table). Grade 3–4 treatment-related adverse events occurred in 18.2% and 7.2% of patients in the NIVO and PBO arms, consistent with the primary analysis. Overall survival will be assessed at a future database lock. Conclusions: With extended follow-up, NIVO continued to show DFS, NUTRFS, and DMFS benefits versus PBO. The hazard ratio (HR) for DFS and NUTRFS in PD-L1 ≥ 1% patients and for DMFS in both ITT and PD-L1 ≥ 1% patients also continued to improve versus the primary analysis. No new safety signals were identified. These results further support adjuvant NIVO as a standard of care for high-risk MIUC after radical resection. Clinical trial information: NCT02632409 . [Table: see text]