Abstract
Advanced or metastatic breast cancer is an incurable disease with high mortality rate worldwide and about 20% of breast cancers overexpress and amplify the human epidermal growth factor receptor 2 (HER2). Achievements in targeted therapy have benefited people during the past decades. Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate playing a powerful role in anti-tumor activity, not only blocks the HER2 signaling pathways, but also disturbs the microtubule dynamics. To access the efficacy and safety of T-DM1, we analyzed 9 clinical trials on T-DM1. Results showed that fatigue (0.604, 95% CI 0.551, 0.654), nausea (0.450, 95% CI 0.365, 0.537), increased transaminases (0.425, 95% CI 0.353, 0.500) and thrombocytopenia (0.383, 95% CI 0.322, 0.448) occurred more frequently in participants with single T-DM1. In controlled trials, increased transaminases (OR = 4.040, 95% CI 1.429, 11.427), thrombocytopenia (OR = 8.500, 95% CI 3.964, 18.226) and fatigue (OR = 1.288, 95% CI 1.041, 1.593) were statistically significant. Only thrombocytopenia appeared as severe adverse event (grade ≥ 3) in single-arm and control-arm studies. Meanwhile, T-DM1 stabilized cancer and prolonged life with notable improved progression-free survival (PFS) and overall survival (OS). In conclusion, it is a safe and effective agent in advanced or metastatic breast cancer, but should be carefully applied on patients with severe hepatic and neurological disease.
Highlights
T-DM1 is a novel antibody-drug conjugate composed of trastuzumab, derivative of maytansine 1 (DM1) and a non-reducible thioether linker[9,10]
After T-DM1 binds to human epidermal growth factor receptor 2 (HER2), the HER2-T-DM1 complex enters into target cells through receptor-mediated endocytosis and releases DM1, causing cell cycle arrest and apoptosis via the inhibition of microtubule assembly[11,12]
For single-arm trials, we calculated the incidence of adverse events and analyzed 3 articles for progression-free survival (PFS)
Summary
T-DM1 is a novel antibody-drug conjugate composed of trastuzumab, derivative of maytansine 1 (DM1) and a non-reducible thioether linker[9,10]. Trastuzumab itself is a humanized monoclonal antibody targeting on HER2 receptors, stimulating antibody-dependent cell-mediated cytotoxicity (ADCC), inhibiting the PTEN-PI3K/ AKT pathway and inducing apotosis[3,11,12,13]. Were launched in different countries among patients with advanced or metastatic HER2-positive breast cancer. A large-scale trial[15] comparing T-DM1 with lapatinib plus capecitabine among HER2-positive metastatic breast cancer patients indicated that T-DM1 significantly improved the OS and median progression-free survival (PFS). T-DM1 brought clinical benefits to patients, at the same time, the adverse events (AEs) were inevitable. We analyzed published clinical trials to evaluate the odd ratios (ORs) of adverse events and hazard ratios (HRs) for PFS and OS
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