title: Safety and Efficacy of Trastuzumab Emtansine in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: a Meta-analysis.
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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Xuelei
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Chenjing
authors.initials: C
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Jia
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human