Abstract
Purpose: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the cytotoxic agent DM1, is utilized for the management of human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (mBC), after progression on prior trastuzumab. Its regulatory approval preceded the era before pertuzumab approval. In the contemporary era, pertuzumab and/or trastuzumab is employed in routine clinical practice in the first-line (1L) setting. It is therefore relevant to consider currently utilized regimens to confirm their role in current clinical practice. The current study evaluated real-world evidence (RWE) for the efficacy and safety of T-DM1 in HER2-positive mBC and compare with evidence from the clinical trial program.
Methods: Searches were performed in PubMed, Embase, and Cochrane for eligible studies from inception until May 22, 2024. Screening was performed using AccuScreener module of SymproAI online software. Variables of interest included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade ≥3 adverse events (AEs).
Results: Fifty-five publications were identified; 19 from 12 clinical trials and 36 from 34 real-world studies. ORR ranged between 25.0–50.4% (clinical trials) and 14.3–80.0% (real-world studies). Corresponding median PFS was 4.3–9.6 months and 2.8–12.0 months while the median OS was 22.7–34.3 and 12.0–45.0 months, respectively. Furthermore, real-world data suggest the benefit of T-DM1 is more marked in patients without prior pertuzumab. Evidence from both trials and real-world studies support the use of T-DM1 in patients with brain/central nervous system (CNS) metastasis. Safety data from the studies demonstrated a consistent safety profile in terms of AEs (≥grade 3), with thrombocytopenia being the most frequent.
Conclusion: This review demonstrated T-DM1 as an effective treatment for HER2-positive mBC in the second-line (2L) or later setting and has an acceptable safety profile.
Keywords
Breast Cancer, HER2 Gene, Trastuzumab emtansine, Treatment outcome, Brain metastasis