Trastuzumab (Tmab) plus chemotherapy (CT) vs CT alone in the perioperative treatment of HER2-positive gastric cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

e16129 Background: HER2 overexpression occurs in 15-20% of gastric cancers (GC) and is associated with poor prognosis. While Tmab combined with CT improves survival HER2-positive GC, its role in resectable disease remains unclear. We conducted a meta-analysis of RCTs to evaluate the efficacy and safety of Tmab plus CT versus CT alone in the perioperative treatment of in HER2-positive GC and gastroesophageal junction (GEJ) adenocarcinomas. Methods: We systematically searched PubMed, Embase, and Cochrane databases for RCTs comparing Tmab plus CT with CT alone in resectable HER2-positive GC. Outcomes included pathologic complete response (pCR), R0 resection rate, progression-free survival (PFS), overall survival (OS), treatment completion, and diarrhea incidence. Data were pooled using a random-effects model. Heterogeneity was assessed via I² statistics. Analyses were performed using R software v4.3.2. Results: Three RCTs (229 patients) met inclusion criteria. Tmab showed a non-significant reduction in death risk (HR 0.74; 95% CI: 0.44–1.25; p = 0.26; I² = 0%) and PFS (HR 0.72; 95% CI: 0.48–1.06; p = 0.09; I² = 0%). No significant differences were found in pCR (RR 0.24; 95% CI: 0.04–1.45; p = 0.12; I² = 37.3%) or R0 resection rates (RR 1.41; 95% CI: 0.89–2.24; p = 0.15; I² = 0%). Similarly, treatment completion (RR 1.04; 95% CI: 0.95–1.13; p = 0.45; I² = 0%) and diarrhea incidence (RR 1.01; 95% CI: 0.93–1.09; p = 0.84; I² = 0%) were comparable between groups. Heterogeneity was low or absent across all the outcomes. Conclusions: In conclusion, the addition of Tmab to perioperative chemotherapy in HER2-positive resectable GC did not yield statistically significant improvements in survival, pathological response, or surgical outcomes, although the regimen was well tolerated. Further large-scale trials are warranted to better define the role of anti-HER2 therapy in the curative-intent setting.