T-DM1 BETTER THAN DOCETAXEL-TRASTUZUMAB COMBINATION

J Clin Oncol. 2013 Feb 11. [Epub ahead of print]

Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA.

Source

Sara A. Hurvitz, University of California at Los Angeles Jonsson Comprehensive Cancer Center and Translational Oncology Research International, Los Angeles, CA; Luc Dirix, Sint-Augustinus Hospital, Antwerp, Belgium; Judit Kocsis, Semmelweis University Hospital, Budapest, Hungary; Giulia V. Bianchi, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy; Janice Lu, State University of New York at Stony Brook, Stony Brook, NY; Jeferson Vinholes, Clinica de Oncologia, Porto Alegre, Brazil; Ellie Guardino, Chunyan Song, Barbara Tong, Vivian Ng, and Yu-Waye Chu, Genentech, South San Francisco, CA; and Edith A. Perez, Mayo Clinic, Jacksonville, FL.

Abstract

PURPOSETrastuzumab 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 METHODSPatients (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.ResultsMedian 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 40.9%), 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. CONCLUSIONIn 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.