Dual Inhibition of HER2 and VEGF Pathways in Breast Cancer

OBJECTIVES: The vascular endothelial growth factor (VEGF) pathway plays a crucial part in tumor angiogenesis by enhancing the creation of new blood vessels that supply oxygen. Breast cancer cells with overexpressed human epidermal growth factor receptor 2 (HER2) usually produce high levels of VEGF, because HER2 signaling upregulates VEGF expression. We aim to investigate the clinical benefit of VEGF and HER2 inhibitors in the treatment of breast cancer. METHODS: A systematic search for records from inception until January 2025 was conducted in PubMed, Web of Science, MEDLINE, Scopus, and Google Scholar. The primary endpoint of the present review was the overall response rate (ORR), and the secondary endpoints were complete response (CR) and partial response (PR). RESULTS: Five distinct clinical trials enrolling 307 women with HER2-positive breast cancer were included in the present meta-analysis. The pooled analysis revealed that the ORR of breast cancer patients treated with anti-HER2 combined with anti-VEGF was 31.9% (95% CI: 21.6%-44.2%). Moreover, 4.9% of patients treated with anti-HER2 combined with anti-VEGF achieved CR, and 32.6% achieved PR. Data from 2 included trials also showed that patients treated with lapatinib and pazopanib had significantly higher response rates than patients receiving lapatinib alone (OR: 2.21; 95% CI: 1.15-4.22; P = 0.017). CONCLUSIONS: Dual inhibition of HER2 and VEGF demonstrated promising responses, with 31.9% of patients achieving ORR. Furthermore, the combined targeting of HER2 and VEGF, with lapatinib and pazopanib results in better responses than monotherapy targeting of HER2 with lapatinib.