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

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.

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.

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.

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.