Abstract
BACKGROUND: This study aimed to evaluate the safety and efficacy of first-line nivolumab plus chemotherapy for real-world patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (AGC). MATERIALS AND METHODS: This single-institutional retrospective study enrolled patients with HER2-negative AGC who were treated with nivolumab plus chemotherapy between September 2021 and January 2024. Early tumor shrinkage (ETS) and depth of response (DpR) were assessed. RESULTS: There were 136 patients with a median age of 65 years (range 27-83 years); 57% were men, the rate of programmed cell death ligand 1 combined positive score of <1/1-4/≤5 was 32%/38%/30%, respectively, and deficient mismatch repair and/or high microsatellite instability was 7%. At a median follow-up of 14.0 months, the median progression-free survival (PFS) and overall survival (OS) were 7.9 and 21.7 months, respectively. In patients with measurable lesions at baseline, the objective response and disease control rates were 58% and 82%, respectively; the complete response rate was 10%. The median DpR was 45.8%. An increasing DpR was associated with a longer OS. In the exploratory analysis by ETS, both the median PFS [hazard ratio (HR) 0.34; 95% confidence interval (CI) 0.17-0.67; P < 0.01] and OS (HR 0.47; 95% CI 0.21-0.98; P = 0.04) were longer in the ETS group than in the non-ETS group. Immune-related adverse events of any grade occurred in 26% of patients (12% with grades 3-4). CONCLUSIONS: First-line nivolumab plus chemotherapy provides benefits to real-world patients with HER2-negative AGC and implies that the rapidity and magnitude of tumor shrinkage may have a significant impact on the duration of survival.