Emerging Immunotherapy Options in HER-2-PositiveMetastatic Breast Cancer: A Meta-Analysis on Clinical Effectiveness and Safety of T-DM1, Trastuzumab-Pertuzumab, and Trastuzumab Deruxtecan

HER-2-positive metastatic breast cancer (MBC) remains a clinical challenge due to its aggressive nature and resistance to conventional therapies. This meta-analysis compares the clinical effectiveness and safety profiles of three key targeted immunotherapies: trastuzumab emtansine (T-DM1), trastuzumab−pertuzumab, and trastuzumab deruxtecan, focusing on overall survival (OS), progression-free survival (PFS), and adverse event profiles. Eligible studies were retrieved from PubMed and filtered for randomized controlled trials (RCTs) published between January 2019 and June 2024. Nonrandomized studies, reviews, and editorials were excluded. Data from four studies were included in the meta-analysis, which was performed using RevMan software. The findings show that T-DM1 presents a favorable balance between efficacy and safety, particularly in patients with prior trastuzumab-based treatments. While trastuzumab deruxtecan demonstrated superior efficacy in heavily pretreated patients, it was associated with a higher risk of severe adverse events, particularly interstitial lung disease (ILD). Trastuzumab−pertuzumab remains the preferred first-line treatment but shows reduced effectiveness in later treatment lines. Overall, while all three treatment regimens provide significant benefits for patients with HER-2-positive MBC, T-DM1 emerges as a safer option for patients with cardiotoxicity risks. Trastuzumab−pertuzumab offers the best balance between efficacy and safety, while trastuzumab deruxtecan offers superior effectiveness in patients with advanced disease stages. These findings emphasize the importance of personalized treatment plans in optimizing clinical outcomes.