Cisplatin-based neoadj chemo followed by surgery has been a standard of care for eligible pts with MIBC. Neoadj therapy has evolved with the emergence of perioperative checkpoint inhibition. Adjuvant (adj) nivolumab (NIVO) has improved outcomes in high-risk muscle-invasive urothelial carcinoma after surgery. We report the final analysis (FA) of CA017-078, a phase 3 trial of neoadj NIVO + gemcitabine/cisplatin (GC) and adj NIVO vs neoadj GC in pts with MIBC.
Pts with previously untreated MIBC (cT2-T4aN0M0) were randomized to NIVO 360 mg + GC Q3W × 4 cycles, surgery, then adj NIVO 480 mg Q4W × 9 cycles (NIVO+GC/NIVO) or neoadj GC Q3W × 4 cycles, followed by surgery. Randomization was stratified by clinical tumor stage (T2 vs T3/T4a), GFR (50 to < 60 vs ≥ 60 mL/min), and tumor PD-L1 status (≥ 1% vs < 1%/indeterminate). Primary endpoints: event-free survival (EFS) by blinded independent review committee and pathologic complete response (pCR) rate by BICR (measured earlier at FA of pCR). Secondary endpoints: overall survival (OS) and safety.
653 pts were randomized to NIVO+GC/NIVO (n = 325) or GC (n = 328). 76.6%/17.2%/5.5% vs 77.4%/14.9%/6.7% of pts had T2/T3/T4a stage tumors, respectively. With median follow-up of 54.5 mo, EFS did not differ significantly between arms (HR 0.94 [95.74% CI 0.71–1.25]; P = 0.67; median not reached [95% CI not estimable (NE)] for NIVO+GC/NIVO vs 67.6 [63.0–NE] mo for GC). pCR rate did not differ significantly for NIVO+GC/NIVO vs GC (39.1% vs 29.6%; OR 1.54 [99.91% CI 0.88–2.69]). OS was immature at EFS FA (HR 0.88 [95% CI 0.64–1.21] for NIVO+GC/NIVO vs GC). TRAEs (grade ≥ 3) were reported in 45.9% of pts with NIVO+GC/NIVO and 49.5% with GC. Efficacy in relevant clinical and biomarker subgroups (ie, ctDNA) will be presented.
No statistically significant differences in the primary endpoints of EFS and pCR were observed with neoadj NIVO+GC followed by adj NIVO vs GC in pts with resectable MIBC. Safety of NIVO+GC was consistent with the individual agents. While the primary outcomes were not significantly different between arms, the results are important to optimize future management of MIBC.
NCT03661320