Treatment-Related Toxicities of Antibody-Drug Conjugates in Breast Cancer: A Bayesian Network Meta-Analysis.

IntroductionAntibody-drug conjugates (ADCs) are now widely used in breast cancer across multiple disease subtypes. With increasing clinical use, treatment-related toxicities have become an important factor in therapeutic decision-making. However, comparative safety data among ADCs are limited because direct head-to-head trials are lacking.MethodsWe conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials evaluating ADCs in breast cancer, with the literature search updated through March 31, 2025. Treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were classified according to the Common Terminology Criteria for Adverse Events. A Bayesian random-effects network meta-analysis was used to compare toxicity risks across regimens. Odds ratios (ORs) with 95% credible intervals (CrIs) were estimated, and surface under the cumulative ranking curve (SUCRA) values were used as descriptive ranking summaries interpreted alongside the corresponding comparative estimates. The protocol was registered in PROSPERO (CRD42024606194).ResultsSeventeen randomized trials including 8,946 patients and five ADCs-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), and ARX788-were analyzed. SG and T-DXd showed the least favorable hematologic safety profiles, with SUCRA values for anemia/neutropenia of 22.6%/17.4% and 12.0%/27.0%, respectively. T-DM1-based regimens had the highest risk of thrombocytopenia. For gastrointestinal toxicities, SG ranked worst for diarrhea (SUCRA 6.0%), whereas T-DXd was associated with higher risks of nausea (2.2%), vomiting (7.9%), and decreased appetite (8.6%). In analyses of SAEs, SG had the highest rates of anemia (11.7%) and neutropenia (8.5%), while gastrointestinal SAEs occurred more frequently with T-DXd.ConclusionsThis network meta-analysis highlights clinically meaningful differences in ADC safety profiles and may help guide individualized toxicity management in breast cancer. Antibody–drug conjugates (often called ADCs) are a newer type of targeted treatment for breast cancer. These medicines combine an antibody, which helps deliver treatment directly to cancer cells, with a powerful chemotherapy drug. ADCs have improved outcomes for many patients, including those with advanced or difficult-to-treat breast cancer. However, like all cancer treatments, they can cause side effects. Different ADCs are now widely used in clinical practice, but there are few studies directly comparing their safety. To better understand how their side effects differ, we analyzed data from 17 high-quality clinical trials involving nearly 9,000 patients with early-stage or metastatic breast cancer. We compared five commonly used ADCs and standard treatments to evaluate how often patients experienced treatment-related side effects. We found that side effect profiles varied meaningfully between drugs. Some ADCs were more likely to cause low blood counts, which can increase the risk of infection or fatigue. Others were more commonly linked to digestive problems such as nausea, vomiting, or diarrhea. Certain treatments were also associated with higher rates of serious side effects that required medical attention. In contrast, a few newer ADCs appeared to have more favorable overall tolerability. Our findings highlight that not all ADCs have the same safety profile. Understanding these differences can help doctors and patients weigh the potential benefits and risks of each treatment option. This information may support more personalized treatment decisions and improve side effect management in breast cancer care.