• DOI:10.1200/JCO.2012.44.9694
• Corpus ID: 456568

Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

@article{Hurvitz2013PhaseIR,
  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.},
  author={Sara Alsterlind Hurvitz and Luc Y. Dirix and Judit Kocsis and Giulia Valeria Bianchi and Janice M. Lu and Jeferson J.F. Vinholes and Ellie Guardino and Chunyan Song and Barbara Tong and Vivian W. Ng and Y Chu and Edith A. Perez},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  year={2013},
  volume={31 9},
  pages={
          1157-63
        }
}

• S. Hurvitz, L. Dirix, +9 authors E. Perez
• Published 4 February 2013
• Medicine, Biology
• Journal of clinical oncology : official journal of the American Society of Clinical Oncology

PURPOSE
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.

PATIENTS AND 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.

CONCLUSION
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.