Survival benefits of conversion surgery for stage IV gastric cancer patients treated with anti-PD-1 antibody and chemotherapy and/or targeted therapy

Although anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy has shown promising antitumor activity in advanced gastric adenocarcinoma (GC), the evidence of conversion therapy for initially unresectable (Stage IV, AJCC/UICC) GC is limited. This study aimed to clarify the clinical significance of conversion therapy for Stage IV GC patients who underwent first-line anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy. In this prospective single institution cohort study, we analyzed 136 Stage IV GC patients who received first-line anti-PD-1 antibody and chemotherapy and/or target therapy (trastuzumab) between November 2019 and January 2023. In downstaged patients, when preoperative imaging studies, multidisciplinary team (MDT) discussions and analytical evaluations, and staged laparoscopy indicated the possibility of R0 resection, patients were offered radical surgery with patients’ consent. In this study, palliative surgery was not examined. We divided patients into two groups: conversion surgery group and non-surgery group. Ninety-three (68.4%) of 136 patients underwent laparoscopic exploration at their initial visit. All patients underwent at least one treatment cycle, with a median follow-up time of 16.73 months as of January 2023. Of the 136 patients, 60 (44.2%) patients achieved an objective response, including 8 (5.9%) complete response (CR) and 52 (38.3%) partial response (PR), 42 patients (30.8%) achieved conversion surgery. Compared with non-surgery group, surgery group had a significantly better median progression-free survival (PFS) (not reached vs 5.97 months; hazard ratio [HR] 0.21; 95% confidence interval [CI] 0.13–0.33; p < 0.001) and a prolonged overall survival (OS) (not reached vs 13.27 months; HR 0.10; 95% CI 0.06–0.18; p < 0.001). In the surgery group, 41 (97.6%) of 42 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 32 patients gained R0 resection (76.2%), 7 patients (16.7%) achieved pathologic complete response (pCR) and 10 patients (23.8%) reached tumor regression grade (TRG) 0-1. The median disease-free survival (DFS) was 23.3 months. And multivariate analysis associated with PFS among surgery cases identified signet ring cell as an independent adverse prognostic factor (HR 6.29; 95% CI 1.56–25.36). 20 (47.6%) of 42 patients had grade 3–4 treatment-related adverse events (TRAEs). The most common grade 3-4 TRAEs were anemia (26.2%), thrombocytopenia (9.5%), neutropenia (9.5%), leucopenia (7,1%). Surgery-related complications included abdominal abscess (7.1%), pulmonary infection (7.1%), abdominal fluid collection (2.4%), leakage (2.4%). No serious TRAEs or surgery-related complications resulted in termination of treatment or death. Conversion surgery following first-line anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy represented a promising treatment strategy for Stage IV GC patients, with the potential for significant survival benefits for the majority of patients. Further multi-center, prospective clinical studies are necessary to verify.