Icahn School of Medicine at Mount Sinai, New York, NY
Matt D. Galsky , Alfred Alfred Witjes , Jürgen E. Gschwend , Michael Schenker , Begoña Pérez Valderrama , Yoshihiko Tomita , Aristotelis Bamias , Thierry Lebret , Shahrokh F. Shariat , Se Hoon Park , Mads Agerbaek , Gautam Gopalji Jha , Frank Stenner , Santanu Dutta , Federico Nasroulah , Joshua Zhang , Lynne Brophy , Dean F. Bajorin
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.
NIVO No. of events/ no. of patients (%) | NIVO Median (95% CI), mo | PBO No. of events/ no. of patients (%) | PBO Median (95% CI), mo | HR (95% CI) | |
---|---|---|---|---|---|
DFS, ITT | 195/353 (55) | 22.0 (18.8–36.9) | 233/356 (65) | 10.9 (8.3–15.2) | 0.71 (0.58–0.86) |
DFS, PD-L1 ≥ 1% | 61/140 (44) | 52.6 (25.8–NE) | 89/142 (63) | 8.4 (5.6–17.9) | 0.52 (0.37–0.72) |
NUTRFS, ITT | 184/353 (52) | 25.9 (19.4–44.0) | 217/356 (61) | 13.7 (8.4–20.3) | 0.72 (0.59–0.88) |
NUTRFS, PD-L1 ≥ 1% | 60/140 (43) | 52.6 (29.7–NE) | 86/142 (61) | 8.4 (5.6–20.0) | 0.53 (0.38–0.74) |
DMFS, ITT | 155/353 (44) | 47.1 (26.5–NE) | 177/356 (50) | 28.7 (16.6–47.8) | 0.74 (0.60–0.92) |
DMFS, PD-L1 ≥ 1% | 53/140 (38) | NR (44.0–NE) | 68/142 (48) | 20.7 (10.6–NE) | 0.58 (0.40–0.84) |
CI, confidence interval; NE, not estimable, NR, not reached.
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