LBA9_PR Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiation therapy (CRT): First results of the CheckMate 577 study

The risk of recurrence after neoadjuvant CRT followed by surgery (trimodality therapy) remains high in EC/GEJC and there is no established adjuvant treatment. CheckMate 577 is the first global, randomized, double-blind, phase 3 study to report the efficacy and safety of a checkpoint inhibitor in the adjuvant setting after trimodality therapy for EC/GEJC. 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 disease-free survival (DFS). 794 patients were randomized (nivolumab, 532; placebo, 262). Approximately 70% of patients had adenocarcinoma and almost 60% had a pathologic lymph node status ≥ypN1 in both groups. At a pre-specified interim analysis, adjuvant nivolumab showed a statistically significant improvement in DFS vs placebo (HR 0.69 [96.4% CI 0.56 -0.86]; P = 0.0003); median DFS was doubled (22.4 vs 11.0 mo, respectively; Table). The majority of treatment-related adverse events (TRAEs) were grade 1 or 2. The frequency of serious TRAEs and TRAEs leading to discontinuation were ≤ 9% with nivolumab and 3% with placebo (Table). Data including DFS rate and an analysis of DFS across pre-specified subgroups will be presented.Table: LBA9_PREfficacyNivolumabN = 532PlaceboN = 262Median DFS, mo (95% CI)22.4 (16.6–34.0)11.0 (8.3–14.3)HR (96.4% CI; P value)0.69 (0.56–0.86; P = 0.0003)Safety, n (%)N = 532N = 260Any-grade TRAEs376 (71)119 (46)Grade 3–471 (13)15 (6)Serious TRAEs40 (8)7 (3)Grade 3–429 (5)3 (1)TRAEs leading to discontinuation48 (9)8 (3)Grade 3–426 (5)7 (3) Open table in a new tab Adjuvant nivolumab is the first therapeutic to provide a statistically significant and clinically meaningful improvement in DFS vs placebo and a well-tolerated safety profile in patients with resected EC/GEJC, who have received neoadjuvant CRT. These results represent the first treatment advance in many years for these patients, potentially establishing adjuvant nivolumab as a new standard of care.