HER2-Targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: A systematic review and meta-Analysis

Abstract

Background: Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-Targeted therapy on IMD from HER2-positive breast cancer. Methods: We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-Targeted therapy. We pooled outcomes through meta-Analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). Results: A total of 97 studies (37 interventional and 60 observational) were included. HER2-Targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39-0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27-1.02) versus non-Targeted therapy; the intracranial objective response rate was 19% (95% CI, 12-27%), intracranial disease control rate 62% (95% CI, 55-69%), intracranial complete response rate 0% (95% CI, 0-0.01%), and grade 3+ adverse event rate 26% (95% CI, 11-45%). Risk of bias was high in 40% (39/97) of studies. Conclusion: These findings support a potential role for systemic HER2-Targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.