Defining the role of HER2-targeted therapy as perioperative treatment in HER2-positive gastric and gastro-oesophageal junction cancers: protocol for a systematic review and an individual patient data meta-analysis

The role of HER2-targeted therapy in the perioperative treatment of HER2-positive gastric and gastro-oesophageal junction (GEJ) cancer remains unclear, largely due to inconsistent results and the limited statistical power across individual clinical trials. This systematic review and individual patient data meta-analysis aims to evaluate the impact of HER2-targeted therapy on pathological tumour response and survival outcomes. This review will include randomised controlled trials and single-arm interventional trials evaluating the perioperative HER2-targeted therapy plus chemotherapy in HER2-positive resectable gastric and GEJ cancer. The main comparison will be HER2-targeted therapy plus chemotherapy versus chemotherapy alone, where an internal control arm is available. A comprehensive literature search will be conducted in MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, and major international oncology conferences proceedings. The primary outcomes are pathological tumour response and time-to-event outcomes, including progression-free survival and overall survival. A one-stage meta-analysis using individual participant data will be performed to assess treatment effects, with prespecified subgroup analyses exploring heterogeneity according to sex, tumour site, geographical region, histological subtype, HER2 status and chemotherapy regimen. By integrating individual-level data across studies, this IPD meta-analysis will provide more precise evidence on the efficacy and safety of adding HER2-targeted therapy to perioperative chemotherapy in HER2-positive gastric and GEJ cancer. The findings are expected to support the design of future clinical trials and contribute to the future development of perioperative treatment strategies for this patient population. PROSPERO CRD420251248294.