Safety and efficacy of first-line nivolumab plus chemotherapy for HER2-negative advanced gastric cancer in real-world patients: Updated analysis.

341 Background: Based on the results of CheckMate-649 and ATTRACTION-4, nivolumab plus chemotherapy is the new standard of care as first-line treatment for patients with HER2-negative advanced gastric cancer (AGC) regardless of PD-L1 combined positive score (CPS) status in Japan. This study aimed to evaluate the safety and efficacy of this regimen in real-world patients with HER2-negative AGC with a longer follow-up. Methods: In this single-institutional retrospective study, patients with HER2-negative AGC who were treated with first-line nivolumab plus chemotherapy between September 2021 and April 2024 were consecutively enrolled and evaluated. Early tumor shrinkage (ETS) was defined as ≥20% tumor reduction at 8 ± 2 weeks. Results: Of 151 patients, median age was 66 years (range, 27–83); 58% were male; 81% had diffuse-type histology; the peritoneal metastasis was seen in 60%; PD-L1 CPS of <1, 1≤/<5, 5≤ was 30%/41%/29%; deficient mismatch repair and/or high microsatellite instability was 7%. At a median follow-up of 14.2 months, the median overall survival (OS) and progression-free survival (PFS) were 21.7 months (95% confidence interval [CI] 14.4–26.2) and 7.7 months (6.4–9.6), respectively. The median OS according to CPS subgroups (<1, 1≤/<5, 5≤) were 21.7 / not reached (NR) /25.0 months, respectively (log-rank P = 0.55). In patients with measurable lesions at baseline according to RECIST ver 1.1, the objective response rate and disease control rate were 62% and 87%, respectively, with a complete response rate of 10%. In the exploratory analysis by ETS, both median PFS and OS were significantly longer in the ETS group compared to the non-ETS group (PFS, NR vs. 6.2 months; hazard ratio [HR] 0.35; 95% CI 0.17–0.68; P = 0.001) (OS, 25.0 vs. 11.7 months; HR 0.44; 95% CI 0.20–0.93; P = 0.03). The immune-related adverse events (irAEs) of any grade were observed in 26% (grade 3–4 irAEs 12%), whereas no treatment-related death was documented. Conclusions: The updated analysis suggests that first-line nivolumab plus chemotherapy provides benefit in real-world patients with HER2-negative AGC regardless of PD-L1 status, and suggests that the magnitude of ETS may predict a significant impact on the duration of survival.