Efficacy and safety of trastuzumab deruxtecan in treating human epidermal growth factor receptor 2-low/positive advanced breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: A novel antibody-drug conjugate, trastuzumab deruxtecan is a combination of a human epidermal growth factor receptor 2 (HER2)-targeting antibody and DNA topoisomerase I inhibitor used to treat HER2-low/positive advanced breast cancer. To determine its safety and efficacy in treating HER2-low/positive advanced breast cancer, we performed a meta-analysis of several randomized clinical trials (RCTs) including DESTINY-Breast02 (NCT03523585), DESTINY-Breast03 (NCT03529110), and DESTINY-Breast04 (NCT03734029).

METHODS: We searched PubMed, Embase, and the Cochrane Library for RCTs on the efficacy and safety of trastuzumab deruxtecan that were published before May 2023. The efficacy endpoints included median progressive-free survival (PFS), overall survival (OS), duration of response (DOR), overall response rate (ORR), and clinical benefit rate (CBR). The safety endpoints included treatment-related adverse events. Statistical analyses were performed using RevMan 5.4 software. To ensure transparency, this study was registered on the International Prospective Register of Systematic Reviews website (CRD42023414170).

RESULTS: Three RCTs involving 1689 patients were included. Compared with physician-recommended and conventional treatments, trastuzumab deruxtecan exhibited statistically significant improvements in PFS, overall response rate, and clinical benefit rate. The median OS and duration of response failed to be combined; however, the analyzed studies showed that they were longer. The incidence of adverse events was generally higher with trastuzumab deruxtecan than with physician-recommended or conventional treatments.

CONCLUSION: The results of this study suggest that trastuzumab deruxtecan is more effective in treating HER2-low/positive advanced breast cancer than physician-recommended or conventional treatments. However, trastuzumab deruxtecan-related adverse drug reactions should be closely monitored because of its higher incidence of adverse events.