Adverse events and impact on quality of life of antibody-drug conjugates in the treatment of metastatic breast cancer: A systematic review and meta-analysis

Abstract

Background Antibody-drug conjugates are novel effective therapies for metastatic breast cancer. Nevertheless, their toxicity profile can significantly affect patients' quality of life over time. Methods This is a systematic review and meta-analysis of randomized controlled trials of antibody-drug conjugates currently approved for the treatment of metastatic breast cancer [trastuzumab-emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab-govitecan (SG)] versus standard therapy to evaluate the risk of adverse events, discontinuation rate due to toxicity, impact on quality of life according to EORTC QLQ-C30 scale and subdomains. Relative risks (RR) and hazard ratios (HR) with 95% CIs were calculated using random effects models. Results Nine trials with a total of 5753 patients were included. The most common adverse events of any grade for T-DM1 included thrombocytopenia (RR 7.14, 95% CI 4.13–12.36) and increased alanine-transaminase (ALT) (RR 2.04, 95% CI 1.43–2.91), for T-DXd were nausea (RR 2.39, 95% CI 1.90–3.00) and anemia (RR 1.55, 95% CI 1.27–1.90), while for SG were neutropenia (RR 1.30, 95% CI 1.14–1.49), diarrhea (RR 3.62, 95% CI 2.97–4.42) and nausea (RR1.90, 95% CI 1.65–2.19). Severe adverse events such as interstitial lung disease and left ventricular dysfunction were peculiar of T-DXd. Antibody-drug conjugates significantly delayed clinical deterioration of global health status by EORTC QLQ-C30 (HR .71, 95% CI .59–.86), physical, emotional and social functioning, pain and fatigue symptoms. Conclusions This meta-analysis offers consolidated data on adverse events associated with antibody-drug conjugates and their effects on patients' quality of life, emphasizing differences based on the specific agent. These findings underscore the critical need for effective strategies to prevent, diagnose and manage these toxicities.