Dual therapy with HER2-inhibitors (Pertuzumab and Trastuzumab) in Gastric or Gastroesophageal Tumors: A Systematic Review and Meta-analysis

Abstract

Background. The benefit of adding dual HER2 inhibition with Pertuzumab (P) and Trastuzumab (T) to chemotherapy (cT) in HER2-positive gastric or gastroesophageal junction (GEJ) cancer is not yet fully elucidated. Methods. A systematic search of PubMed, Cochrane Central, Embase, Web of Science, SciELO, and LILACS identified clinical trials investigating adjuvant or neoadjuvant regimens combining (P), (T) and (cT). Hazard ratios (HRs) and odds ratios (ORs) for binary endpoints were calculated, with 95% confidence intervals (CIs). Results. Four clinical trials comprising a total of 1,225 patients were included. Dual HER2 blockade plus (cT) showed a significant benefit in survival analysis (HR 0.77, 95% CI 0.69-0.86), especially in terms of overall survival (HR 0.78, 95% CI 0.61-0.99) and progression-free survival (HR 0.73, 95% CI 0.62-0.85). Pathological response rates were higher compared with (cT) alone (OR 1.62, 95% CI 0.98–2.66). Treatment was associated with an increased overall adverse event rate (OR 1.48, 95% CI 1.32-1.66), particularly any-grade diarrhea, hypokalemia, fatigue, and pulmonary infection. Serious adverse events, including deaths and complications, were not significantly different (OR 0.87, 95% CI 0.51-1.49). Conclusions. This systematic review and meta-analysis of clinical trials demonstrates that adding (P), (T) and (cT) improves survival and pathological response in HER2-positive gastric and GEJ tumors, with a manageable safety profile.