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

[BACKGROUND] Although the emergence of immunotherapy has benefited patients with advanced gastric cancer (AGC), the magnitude of the benefit among real-world patients with HER2-negative AGC remains unclear.

[OBJECTIVES] The current study aimed to evaluate the treatment features across various immunotherapy approval periods and investigate the utility of immunotherapy for patients with HER2-negative AGC in daily practice.

[DESIGN] Retrospective observational study.

[METHODS] We retrospectively evaluated the clinical outcomes of patients with HER2-negative AGC who received first-line platinum-based chemotherapy between 2011 and 2023 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 patients were enrolled ( = 477, 344, and 128 for Groups A, B, and C, respectively). Patient characteristics were comparable between the three groups, except for the proportion of those aged ⩾75 years ( = 0.002), prior gastrectomy ( = 0.03), and liver metastases ( = 0.0005). The median overall survival (OS) was 16.2, 15.2, and 21.3 months in Groups A, B, and C, respectively, with no significant difference between the groups (log-rank  = 0.50). Patients who received first-line immunotherapy plus chemotherapy ( = 173) showed significantly better OS than did those who did not receive any immunotherapy-containing treatment from 2011 to 2017 ( = 382; hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.61-0.99;  = 0.04). Multivariate analysis showed that the use of first-line immunotherapy was not significantly associated with worse OS, whereas the use of any-line immunotherapy was significantly associated with prognosis (HR, 0.54; 95% CI, 0.47-0.63;  < 0.0001). The proportion of patients receiving any second-line treatment was comparable between the groups: 76%, 80%, and 71%, respectively.

[CONCLUSION] Our study suggests that immunotherapy has a moderate impact on improving the survival of real-world patients with HER2-negative AGC, highlighting the need for appropriate treatment strategies, including efforts to identify biomarkers and the development of other agents.