Safety and efficacy of first-line nivolumab plus chemotherapy for HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: real-world data analysis

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.