Comparative Efficacy and Safety of Antibody–Drug Conjugates Versus Standard Chemotherapy in Metastatic Breast Cancer: A Comprehensive Systematic Review and Meta-Analysis

TL;DR

Antibody-drug conjugates (ADCs) are more effective and safer than standard chemotherapy for treating metastatic breast cancer, offering better survival and fewer severe side effects.

Contribution

This study provides a comprehensive meta-analysis comparing ADCs and chemotherapy in metastatic breast cancer, highlighting ADCs' superior efficacy and tolerability.

Findings

ADCs significantly improved overall survival and objective response rates compared to chemotherapy.

ADCs showed comparable progression-free survival and no increase in severe adverse events.

ADCs had fewer severe hematologic and gastrointestinal toxicities but specific risks like interstitial lung disease.

Abstract

Antibody-drug conjugates (ADCs) represent a novel class of therapeutics that link monoclonal antibodies to potent cytotoxic drugs, enabling targeted delivery and reduced systemic toxicity compared with conventional chemotherapy. In metastatic breast cancer (MBC), ADCs have emerged as an important treatment option across human epidermal growth factor receptor 2 (HER2)-positive, HER2-low, and triple-negative subtypes. This systematic review and meta-analysis evaluated the efficacy and safety of ADCs compared with standard chemotherapy by analyzing data from nine randomized controlled trials including 3,498 patients. The pooled results demonstrated that ADCs significantly improved overall survival (OS) and objective response rates while maintaining comparable progression-free survival and showing no increase in grade 3 or higher adverse events. Heterogeneity was low for OS but higher for response rates, reflecting variability among drug types and patient populations. Safety analyses showed that ADCs were generally well tolerated, with fewer severe hematologic and gastrointestinal toxicities than chemotherapy, although specific toxicities such as interstitial lung disease with trastuzumab deruxtecan require ongoing monitoring. Overall, the evidence confirms that ADCs provide superior therapeutic benefits and better tolerability than conventional chemotherapy in MBC, marking a significant advance toward more precise and effective systemic treatment strategies that improve survival and quality of life for patients with advanced disease.

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