Effectiveness and safety of ADCs in advanced and metastatic breast cancer: a systematic review of real-world data

Background: Breast cancer (BC) remains one of the most common cancers in the global population. Traditional treatments such as surgery, chemotherapy, and hormone therapy have significantly improved survival, but challenges remain, especially in advanced and metastatic stages of the disease. Recent progress in precision medicine and targeted treatments has significantly influenced how BC is managed. Among these innovations, antibody-drug conjugates (ADCs) have emerged as an important therapeutic option for individuals with advanced or metastatic BC (aBC, mBC), offering greater specificity and reduced systemic toxicity relative to traditional treatments. As these therapies become more widely used, real-world data (RWD) is essential to understand how they perform outside the controlled environment of clinical trials (CTs). This systematic review aims to examine the real-world efficacy and safety of FDA-approved ADCs in aBC and mBC in post-approval years to uncover trends in patient subgroups not represented in CTs and highlight the role of RWD in shaping treatment decisions. A comprehensive systematic literature review of the PubMed database was performed to identify studies that utilized RWD to evaluate the efficacy and safety of ADCs in aBC and mBC. The main outcomes assessed for effectiveness were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), endpoints commonly used in oncology research. Safety outcomes were measured in relation to adverse events (AEs) and discontinuation rates (DRs). Thirty-one real-world studies were included in the systematic review. All three ADCs showed consistent effectiveness across various subtypes, including HER2-positive, HER2-low, and triple-negative disease. Outcomes such as ORR, PFS, and OS were generally in line with pre-marketing CT data. Notably, many studies assessed cohorts underrepresented in pivotal trials demonstrating promising results that support ADC use in more complex clinical scenarios. Such cohorts include patients pretreated with pertuzumab, those with brain metastases (mets), and heavily pretreated individuals. Safety profiles were manageable and comparable to those reported in pre-marketing CTs. No treatment related deaths were reported in real world settings. ADCs are effective and well-tolerated in real-world settings. Real-world outcomes remained strong, confirming the value of ADCs in everyday practice, despite being administered to a more diverse patient population compared to pre-marketing CTs. However, further research is needed to validate the findings observed in underrepresented subgroups to better inform decision-making in the future.