Hyperthermia enhances the efficacy of PD-1 inhibitor plus chemotherapy in PD-L1 CPS-negative advanced gastric cancer.

Background: Advanced gastric cancer with negative PD-L1 combined positive score (CPS) responds poorly to immunotherapy. This study investigated the efficacy of hyperthermia combined with a PD-1 inhibitor and chemotherapy in this patient population. Methods: In this retrospective study, 72 patients with PD-L1 CPS-negative advanced gastric cancer were enrolled. 37 received hyperthermia plus PD-1 inhibitor and SOX chemotherapy, while 35 received PD-1 inhibitor and chemotherapy alone. Propensity score matching (PSM) was applied. Progression-free survival (PFS) was the primary endpoint. Adverse events and circulating tumor cell dynamics were also assessed. Results: After PSM, baseline characteristics were well-balanced. The CIH group showed significantly prolonged PFS compared to the CI group, both before and after matching (P = 0.00037 and P = 0.0011, respectively). The CIH group also had a significantly lower incidence of fatigue and anorexia (P<0.05). Although circulating tumor cell (CTC) counts increased in both groups after treatment, the post-treatment count and the magnitude of increase were significantly greater in the CIH group (P<0.001), potentially indicating enhanced therapy-induced immune activation and tumor cell death. Conclusion: The addition of hyperthermia to PD-1 inhibitor and chemotherapy significantly improves PFS and reduces specific adverse events in patients with PD-L1 CPS-negative advanced GC. This distinct CTC dynamic change, although still requiring further verification, may offer a potential mechanistic insight into the significant efficacy of this combined strategy.