title: Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.
abstract: OBJECTIVE
  Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting.
  
  
  METHODS
  Patients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life.
  
  
  RESULTS
  Median PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95% CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0% (95% CI, 45.5% to 69.2%) with HT and 64.2% (95% CI, 51.8% to 74.8%) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade ≥ 3 adverse events (AEs; 46.4% v 90.9%), AEs leading to treatment discontinuations (7.2% v 34.8%), [corrected] and serious AEs (20.3% v 25.8%). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms.
  
  
  CONCLUSIONS
  In this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.
authors: University of California, Los Angeles Jonsson Comprehensive Cancer Center and Translational Oncology Research International, Los Angeles, CA, USA.
authors: Sara A
authors: SA
authors: Hurvitz
authors: Luc
authors: L
authors: Dirix
authors: Judit
authors: J
authors: Kocsis
authors: Giulia V
authors: GV
authors: Bianchi
authors: Janice
authors: J
authors: Lu
authors: Jeferson
authors: J
authors: Vinholes
authors: Ellie
authors: E
authors: Guardino
authors: Chunyan
authors: C
authors: Song
authors: Barbara
authors: B
authors: Tong
authors: Vivian
authors: V
authors: Ng
authors: Yu-Waye
authors: YW
authors: Chu
authors: Edith A
authors: EA
authors: Perez
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D043823:Taxoids / Q000008:administration & dosage*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077143:Docetaxel; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human