Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): First results of overall survival (OS) from CheckMate 577.

4000 Background: At 24.4-month (mo) median follow-up, adjuvant nivolumab demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) vs placebo with a well-tolerated safety profile in patients (pts) with resected EC/GEJC with residual pathologic disease following neoadjuvant CRT and surgery in the primary analysis from the global, phase 3 CheckMate 577 study (NCT02743494). We report the final analysis of the hierarchically tested secondary endpoint of OS along with longer follow-up of DFS. Methods: Adults with resected (R0) stage II/III EC/GEJC who received neoadjuvant CRT and had residual pathologic disease were randomized 2:1 to nivolumab 240 mg or placebo Q2W for 16 weeks, followed by nivolumab 480 mg or placebo Q4W. Maximum treatment duration was 1 year. The primary endpoint was DFS. OS was a secondary endpoint, and exploratory endpoints included safety, distant metastasis-free survival (DMFS), and progression-free survival on subsequent systemic therapy (PFS2). Results: 794 pts were randomized (nivolumab, n = 532; placebo, n = 262). With a median follow-up of 78.3 (range, 60.1–96.6) mo, adjuvant nivolumab continued to show DFS benefit vs placebo (HR 0.76 [95% CI 0.63–0.91]; Table). Median OS was numerically longer with nivolumab vs placebo (51.7 vs 35.3 mo), although the difference was not statistically significant (HR 0.85 [95.87% CI 0.70–1.04]; P = 0.1064; Table). OS rates at 3 and 5 years with nivolumab vs placebo were 57% vs 50% and 46% vs 41%, respectively. OS subgroup analyses will be presented. Clinically meaningful improvement in DMFS with nivolumab vs placebo was maintained (Table). PFS2 favored nivolumab vs placebo (HR 0.81 [95% CI 0.67–0.98]). In the nivolumab group, 46% of pts received subsequent therapy vs 60% in the placebo group; 5% vs 15% received subsequent immunotherapy. No new safety signals were identified. Conclusions: Adjuvant nivolumab demonstrated sustained long-term DFS benefit and numerical improvement in OS vs placebo in pts with resected EC/GEJC and residual pathologic disease following neoadjuvant CRT. The safety profile of adjuvant nivolumab remained well-tolerated with longer follow-up. These results further support the use of adjuvant nivolumab in this pt population. Clinical trial information: NCT02743494 . Efficacy Nivolumab(n = 532) Placebo(n = 262) Median DFS (95% CI), mo 21.8 (16.6–29.7) 10.8 (8.3–14.3) HR (95% CI) 0.76 (0.63–0.91) Median OS (95% CI), mo 51.7 (41.0–61.6) 35.3 (30.7–48.8) HR (95.87% CI; P value) 0.85 (0.70–1.04; P = 0.1064) Median DMFS (95% CI), mo 27.3 (21.4–36.0) 14.6 (10.9–20.3) HR (95% CI) 0.75 (0.62–0.90) Safety, n (%) n = 532 n = 260 Any-grade/grade 3–4 TRAEs 379 (71)/75 (14) 124 (48)/17 (7) Any-grade/grade 3–4 TRAEs leading to discontinuation 48 (9)/26 (5) 8 (3)/7 (3) TRAE, treatment-related adverse event.