Dual inhibition of HER2 and VEGF pathways in breast cancer: A meta-analysis of outcomes.

Abstract

e13026 Background: 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 and nutrients to malignancies. Breast cancer cells with overexpressed human epidermal growth factor receptor 2 (HER2) usually produce high levels of VEGF because HER2 signaling upregulates VEGF expression, which generates a feedback loop that promotes tumor progression. Therefore, this cross-talk between VEGF and HER2 pathways suggests the need for dual inhibition to prevent tumor growth signals and angiogenesis simultaneously. Methods: To investigate the clinical benefit of VEGF inhibitors combined with HER2 inhibitors in the treatment of breast cancer. A systematic search for records authored in English and published from January 1990 until January 2025 was conducted in PubMed, Web of Science, MEDLINE, Scopus, and Google Scholar. Clinical trials that evaluated the outcomes of VEGF inhibitors combined with HER2 inhibitors alone without chemotherapy and other cancer treatments were included. 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 trials included adult women with advanced/metastatic HR+ breast cancer, locally advanced stage III/IV HR+ breast cancer, as well as women with relapsed or refractory HER2 positive breast cancer. Out of the Her2-positive cohort, 47% were HR+, and 53% were HR-. The pooled analysis revealed that the ORR of breast cancer patients treated with anti-HER2 combined with anti-VEGF was 31.9% (95% confidence interval (CI): 21.6% to 44.2%). Moreover, 4.9% of patients treated with anti-HER2 combined with anti-VEGF achieved CR, and 32.6% achieved PR. Data from two 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 to 4.22; p = 0.017). Conclusions: Overall, dual inhibition of HER2 and VEGF without chemotherapy is a promising therapeutic strategy for patients with breast cancer, especially those with HER2-overexpressing breast cancer.