T-DM1 EFFECTIVE FOR HER2+ REFRACTORY BREAST CANCER

J Clin Oncol. 2012 May 29. [Epub ahead of print]

A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2 -Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine.

Krop IE, Lorusso P, Miller KD, Modi S, Yardley D, Rodriguez G, Guardino E, Lu M, Zheng M, Girish S, Amler L, Winer EP, Rugo HS.

Source

Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Patricia LoRusso, Karmanos Cancer Institute, Detroit, MI; Kathy D. Miller, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Shanu Modi, Memorial Sloan-Kettering Cancer Center, New York, NY; Denise Yardley, Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN; Gladys Rodriguez, South Texas Oncology/Hematology, San Antonio, TX; Ellie Guardino, Michael Lu, Maoxia Zheng, Sandhya Girish, and Lukas Amler, Genentech, South San Francisco, CA; and Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA.

Abstract

PURPOSETo determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies.Patients and methodsIn this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety.ResultsAmong 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%). CONCLUSIONT-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population.