The role of immunotherapy for real-world patients with HER2-negative advanced gastric cancer between 2011-2023.

404 Background: Although the appearance of immunotherapy has apparently brought benefits for all patients (pts) with advanced gastric cancer (AGC), the magnitude of the benefit in real-world pts with HER2-negative AGC has not been fully investigated. Methods: We conducted a retrospective study on pts with HER2-negative AGC who received first-line platinum-based chemotherapy between 2011 and 2023. We evaluated the clinical outcomes across different periods of immunotherapy approval in Japan: Group A (pre-immunotherapy approval): 2011-2017, Group B (approved for third-line treatment or later): 2018-2021, and Group C (approved for first-line treatment): 2022-2023. Results: A total of 949 pts were enrolled (A: n = 477; B: n = 344; C: n = 128). Patient's characteristics were comparable except for the proportion of those with age ≥75 years (P = 0.002), prior gastrectomy (P = 0.03), and liver metastases (P < 0.001). The median overall survival (OS) was 16.2, 15.2, and 21.3 months in group A, B, and C, respectively, with no significant difference between groups (log-rank P = 0.50). Pts who had received first-line immunotherapy plus chemotherapy (n = 173) showed significantly improved OS compared with pts without having received any immunotherapy-containing treatment at 2011-2017 (n = 382) (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.61-0.99; P = 0.04). In the multivariate analysis, the use of immunotherapy at first-line treatment was not significantly associated with worse OS, whereas the use of immunotherapy at any lines was prognostic (HR, 0.54; 95% CI, 0.41-0.71; P < 0.0001). The proportion of pts who had received any second-line treatment was comparable among groups: 76%, 80%, and 71%, respectively. Conclusions: Our study suggests that the immunotherapy might partially have an impact on the survival improvement of real-world pts with HER2-negative AGC, which calls for the need for appropriate treatment strategies, including other agents.