Article first published online: 30 MAY 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 23, pages 5733–5740, 1 December 2012
How to Cite
Beeram, M., Krop, I. E., Burris, H. A., Girish, S. R., Yu, W., Lu, M. W., Holden, S. N. and Modi, S. (2012), A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer. Cancer, 118: 5733–5740. doi: 10.1002/cncr.27622
Support for third-party writing assistance for this manuscript was provided by Genentech, Inc.
- Issue published online: 19 NOV 2012
- Article first published online: 30 MAY 2012
- Manuscript Accepted: 29 MAR 2012
- Manuscript Revised: 27 MAR 2012
- Manuscript Received: 15 FEB 2012
- trastuzumab emtansine;
- breast cancer;
- antibody-drug conjugate;
We conducted a phase 1, multicenter, open-label, dose-escalation study (TDM3569g) to assess the safety, tolerability, and pharmacokinetics of single-agent trastuzumab emtansine (T-DM1) administered weekly and once every 3 weeks in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab. The weekly dose results are described here.
Patients were administered escalating doses of T-DM1 weekly, starting at 1.2 mg/kg. Additional patients were enrolled at the maximum tolerated dose (MTD) to better characterize tolerability and pharmacokinetics.
Twenty-eight patients received weekly T-DM1, and the MTD was determined to be 2.4 mg/kg. In general, T-DM1 was well tolerated, requiring few dose modifications or discontinuations because of adverse events (AEs). Grade ≥3 AEs were reported in 19 patients (67.9%); treatment-related AEs occurred in 25 (89.3%) patients. Exposure to weekly T-DM1 was dose-proportional at ≥1.2 mg/kg, and accumulation of T-DM1 and total trastuzumab was observed. Objective partial tumor responses were reported in 13 (46.4%) patients; the median duration of response was 18.6 months, and the 6-month clinical benefit rate was 57.1%.
The results suggest that a weekly dose of T-DM1 2.4 mg/kg has antitumor activity and is well tolerated in patients with HER2-positive metastatic breast cancer. Cancer 2012. © 2012 American Cancer Society.