Conversion Surgery After Trastuzumab-Based Chemotherapy and Immunotherapy for Stage IV HER2-Positive Gastric Cancer: A Retrospective Multicenter Cohort Study

Background. The efficacy and safety of conversion surgery after immunotherapy combined with trastuzumab-based chemotherapy for patients with stage IV human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) remains unclear. Methods. This retrospective multicenter study included patients with stage IV HER2-positive GC treated between February 2012 and October 2024 across three centers in China. Eligible patients had histologically confirmed HER2-positive GC with unresectable stage IV disease treated with trastuzumab-based chemotherapy and/or immunotherapy. Conversion surgery was performed for patients who achieved substantial tumor shrinkage enabling R0 resection. Results. Among 232 patients, 114 received chemotherapy combined with trastuzumab alone, whereas 118 were treated with chemotherapy plus immunotherapy and trastuzumab, 50 of whom subsequently underwent conversion surgery. In the cohort receiving chemotherapy and trastuzumab alone, the median progression-free survival (PFS) was 8.2 months (95 % confidence interval [CI], 6.2-10.2 months), and the median overall survival (OS) was 13.9 months (95 % CI, 10.8-17.1 months). The patients who underwent conversion surgery exhibited significantly longer PFS (37.7 vs 10.8 months; P < 0.001) and OS (50.9 vs 22.0 months; P < 0.001) than the non-surgical patients treated with immunotherapy. Conclusions. Preoperative trastuzumab-based chemotherapy combined with immunotherapy followed by conversion surgery significantly improves survival outcomes for patients with stage IV HER2-positive GC.