Efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancer (MBC): a meta-analysis of randomized controlled trial

Abstract

// Hongjing Yan 1 , Kewei Yu 2 , Kaile Zhang 3 , Linxia Liu 4 and Yue Li 5 1 Department of Microbial Testing, Minhang District Centers for Disease Control and Prevention, Shanghai 201101, China 2 Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China 3 Department of Urology, Shanghai Sixth People’s Hospital, Shanghai 200233, China 4 Shanghai University of Medicine and Health Sciences, Shanghai 201318, China 5 Department of Immunization Program, Hongkou District Centers for Disease Control and Prevention, Shanghai 200082, China Correspondence to: Yue Li, email: liyueok624@163.com Keywords: trastuzumab emtansine, HER2-positive, breast cancer, meta-analysis Received: June 28, 2017      Accepted: September 29, 2017      Published: November 01, 2017 ABSTRACT Aims: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate against human epidermal growth factor receptor 2 (HER2), has been used in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We conducted a meta-analysis to evaluate the efficacy and toxicity of T-DM1 for the treatment of patients with HER2-positive MBC. Materials and Methods: Randomized controlled trials (RCTs), published in Pubmed, Embase, and Web of Science were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with MBC who were treated with T-DM1. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95% confidence intervals (CIs). Results: A total of 5 RCTs involving 3,720 patients met the inclusion criteria and were included in this meta-analysis. T-DM1 significantly prolonged PFS (HR = 0.73, 95% CI: 0.61, 0.86; P < 0.05), OS (HR = 0.68, 95% CI: 0.62, 0.74; P < 0.05), but it did not increase ORR (RR = 1.25, 95% CI: 0.94, 1.66; P = 0.148). Subgroup analysis indicated that T-DM1 significantly improved PFS when it was used as first-line (HR = 0.86, 95% CI: 0.74, 1.00; P < 0.05) or non-first-line treatment (HR = 0.65, 95% CI: 0.53, 0.81; P < 0.05). T-DM1 was associated with more frequent adverse events, including fatigue, elevated ALT, elevated AST, and thrombocytopenia, than other anti-HER2 therapies. Conclusions: Based on the current evidence, T-DM1 significantly prolonged PFS and OS with a tolerated toxicity than other anti-HER2 therapies in patients with HER2-positive MBC. These findings confirm the use of T-DM1 for the treatment of patients with HER2-positive MBC. Further well-designed, multi-center RCTs needed to identify these findings.