Treatment-related toxicities of antibody-drug conjugates in breast cancer: A Bayesian network meta-analysis.

e15015 Background: Antibody-drug conjugates (ADCs) have demonstrated significant efficacy in treating patients with breast cancer. However, the toxicity variations between these agents are not yet thoroughly elucidated. This study aims to systematically compare the toxicity profiles of various ADCs used in breast cancer therapy to better inform clinical decision-making. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published by September 2024. Treatment-related adverse events (TRAEs) of the investigational ADCs and standard of care control were classified into systemic categories based on Common Terminology Criteria for Adverse Events. Bayesian models were employed to facilitate the indirect comparisons of TRAEs associated with different ADCs and reported using surface under the cumulative ranking curve (SUCRA) values. The study protocol was prospectively registered on PROSPERO (CRD42024606194). Results: A total of 9307 patients in 17 RCTs of five different ADCs (ado-trastuzumab emtansine [T-DM1], sacituzumab govitecan [SG], trastuzumab deruxtecan [T-DXd], datopotamab deruxtecan [Dato-DXd], and ARX788) were included. SG and T-DXd monotherapy were associated with the highest risk of neutropenia/anemia, with SUCRA values of 11.2%/26.7%, and 20.7%/17.1%, respectively. T-DM1-containing regimens had the highest incidence of thrombocytopenia, which was exacerbated when combined with chemotherapy compared to monotherapy. In terms of gastrointestinal (GI) toxicities, SG was associated with the highest risk of diarrhea, followed by comparable risks between T-DM1 combined with chemotherapy and anti-HER2 and chemotherapy combined with dual anti-HER2 therapy. T-DXd was associated with a relatively higher incidence of vomiting (9.5%), while the highest risk of nausea was seen with chemotherapy with dual anti-HER2 therapy and T-DXd. SG and T-DXd were more likely to cause fatigue, decreased appetite, and dermatological disorders, including alopecia, rash, and pruritus, while T-DM1 combined with anti-HER2 therapies was linked a higher risk of pyrexia. T-DM1-containing regimens were also related to liver function test abnormalities, musculoskeletal and neurological disorders. Dato-DXd was associated with a higher risk of fatigue and dermatological toxicities, while ARX788 was associated with the least hematological and GI TRAEs. Conclusions: This Bayesian network meta-analysis highlights significant variability in TRAEs among different ADCs in breast cancer therapy. T-DM1 was primarily associated with thrombocytopenia and hepatic toxicities, while SG and T-DXd were associated with neutropenia, anemia, GI disorders, and dermatological TRAEs. Our findings may help with selection of ADC therapies for patients with breast cancer, facilitating personalized approaches to minimize treatment-related toxicities.