Immune checkpoint inhibitors combined with chemotherapy in conversion therapy for stage IV gastric cancer: a multicenter retrospective cohort study.

[OBJECTIVES] To evaluate the efficacy of combining PD-1 inhibitors with chemotherapy in conversion therapy for patients with stage IV gastric cancer and to determine the populations most likely to benefit from this regimen.

[METHODS] Data from patients with stage IV gastric cancer who received conversion therapy with PD-1 inhibitors combined with chemotherapy between January 2018 and December 2022 at multiple centers were retrospectively reviewed. Patients who underwent conversion surgery were categorized into a surgery group, while those who did not were placed into a palliative group. The survival outcomes between the two groups and the potential biomarkers that may predict the effectiveness of combining PD-1 inhibitors with chemotherapy were analyzed.

[RESULTS] A total of 105 patients were included in the analysis, with 48 patients in the surgery group and 57 patients in the palliative group, resulting in a conversion rate of 45.7%. R0 resection was performed in 40 patients (83.3%) in the surgery group. The median survival time (MST) was not reached in the surgery group, while it was 12.0 months in the palliative group (P < 0.001). There were significant differences in 1-year and 3-year overall survival (OS) between the two groups (1-year OS: 93.7% vs. 45.6%, P < 0.001; 3-year OS: 52.1% vs. 4.0%, P < 0.001). Subgroup analysis revealed that patients with PD-L1 CPS ≥ 1 had significantly higher overall response rates (62.5% vs. 38.5%, P = 0.016) and conversion rates (60.4% vs. 32.7%, P = 0.005). For patients with peritoneal metastasis, a significant survival benefit was observed in those who received HIPEC treatment compared to those who did not (MST: 18.0 months vs. 9.0 months, P = 0.039). The incidence of treatment-related adverse events was similar to previous observations, with no new safety signals identified.

[CONCLUSIONS] The combination of PD-1 inhibitors with chemotherapy in conversion therapy is feasible for patients with stage IV gastric cancer. Individuals who exhibit improved responses to chemoimmunotherapy potentially experience survival benefits, particularly those with PD-L1 positivity.