Review A meta-analysis of the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancers

Background: The purpose of this study was to analyze the efficacy and safety of additional anti-HER2 (human epidermal growth factor receptor 2)-targeting drugs in HER2-positive advanced breast cancers.Methods For this study, the following databases were searched for articles published from its inception until December 2019: PubMed, Web of Science, EBSCO, and Cochrane library, of which the main outcomes were the progression-free survival (PFS) and overall survival (OS). Results: We conducted a meta-analysis and the results showed that additional anti-HER2-targeting drugs improved the HER2-positive advanced breast cancer patients’ PFS (HR: 0.66, p  < 0.001), OS (HR: 0.77, p  < 0.001), respectively. In terms of drug types, the efficacy of lapatinib was the most (HR: 0.53, 95% Cl: 0.39–0.67, p  < 0.001), followed by pertuzumab (HR: 0.72, 95% Cl: 0.55–0.89, p  = 0.001). Trastuzumab benefited the least, with no difference statistical significance (HR: 0.87, 95% Cl: 0.31–1.44, p  = 0.594). In terms of treatment regimen, first-line treatment (HR: 0.67, 95% Cl: 0.52–0.82, p  < 0.001) had a greater benefit than non-first-line treatment (HR: 0.82, 95% Cl: 0.71–0.94, p  = 0.004). The main adverse events (AEs) observed were diarrhea and the main cardiotoxicity observed was decreased ejection fraction. Conclusions: Additional anti-HER2-targting drugs may improve long-term prognosis in HER2-positive advanced breast cancers. Moreover, the AEs were safe and tolerable. Besides, lapatinib had the best benefit, and pertuzumab followed by, trastuzumab had the least benefit in terms of drug selection. From the aspect of treatment, it recommended significantly to use anti-HER2-targeting drugs in first-line therapy based on our research in HER2-positive advanced breast cancers.