Background: Antibody-drug conjugates (ADCs), as a new type of targeted drug, have been widely used in breast cancer patients in recent years. However, while achieving better efficacy, its hepatotoxicity should not be ignored.
Objectives: To clarify the incidence of hepatotoxicity associated with ADCs and compare the incidence of hepatotoxicity of ADCs with different drugs.
Design: We performed a systematic review and meta-analysis to summarize the clinical trials and combined the data using meta-analysis.
Methods: We searched the PubMed, Embase, and Web of Science databases up to March 12, 2023. The primary outcome was the incidence of ADC-related hepatotoxicity in breast cancer patients. The data were merged using Stata 17.0 software.
Results: ADCs caused a high incidence of all grades of hepatotoxicity. Sacituzumab govitecan caused the highest incidence of all grades of alanine aminotransferase (ALT) elevation at 25.30% (95% confidence interval (CI): 19.29-31.82). Trastuzumab deruxtecan caused the highest incidence of all grades of aspartate aminotransferase (AST) elevation. The highest incidence of AST elevation was 31.89% (95% CI: 18.56-46.85). Conversely, trastuzumab emtansine caused the highest incidence of grade ⩾3 AST and ALT elevation (incidence rates were 3.95% (95% CI: 2.39-5.85) and 3.42% (95% CI: 1.95-5.24), respectively).
Conclusion: Hepatotoxicity is an adverse reaction that cannot be ignored when ADCs are used for treating breast cancer. Moreover, clinicians should pay more attention to the assessment of patients' liver function and monitoring of liver indices, particularly ALT and AST, when using ADCs.
Keywords: antibody–drug conjugates; breast cancer; hepatotoxicity; meta-analysis.
Antibody-drug conjugates (ADCs) can provide better efficacy for breast cancer patients, but the liver toxicity associated with them should not be underestimated Why was this study conducted? In recent years, ADCs have increasingly been used as targeted agents in breast cancer patients. However, while they provide better efficacy, the hepatotoxicity they produce may affect drug usage and patient prognosis. What did the researchers do? The research team collected studies published before March 12, 2023, extracted relevant hepatotoxicity index results from those studies, regrouped them for analysis, and calculated the incidence of hepatotoxicity caused by ADCs. What did the researchers find? The incidence of hepatotoxicity caused by ADCs was generally high, with trastuzumab emtansine causing the highest incidence of severe hepatotoxicity. Trastuzumab deruxtecan, on the other hand, caused relatively little liver toxicity. What do these findings mean? Our findings suggest that clinicians should closely monitor liver function in breast cancer patients treated with ADCs and promptly assess the extent of liver injury in patients who develop abnormal liver function markers. Dose reduction or discontinuation should be considered when necessary.
© The Author(s), 2024.