• Denise A Yardley, Ian E Krop, Patricia M LoRusso, Musa Mayer, Brian Barnett, Bongin Yoo, and Edith A Perez.
• From the *Breast Cancer Research, Sarah Cannon Research Institute; and †Medical Oncology, Tennessee Oncology, PLLC, Nashville, TN; ‡Dana-Farber Cancer Institute, Boston, MA; §Smilow Cancer Center, Yale University, New Haven, CT; ∥AdvancedBC.org, New York, NY; ¶Genentech, Inc, South San Francisco, CA; and #Mayo Clinic, Jacksonville, FL.
• Cancer J. 2015 Sep 1; 21 (5): 357-64.

PurposeThe antibody-drug conjugate trastuzumab emtansine (T-DM1) has improved outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), as demonstrated in phase III studies. Few data approximating its use in routine clinical practice are available.MethodsThe T-DM1 Patient Access Study was an expanded-access, multicenter study of T-DM1 in US patients with pretreated HER2-positive locally advanced breast cancer or MBC. The primary endpoint was safety. The secondary endpoint was investigator-assessed objective response rate among patients with measurable disease at baseline. Data are presented for the first 215 enrolled patients.ResultsThe median number of prior systemic MBC agents was 8 (range, 3-23). At baseline, median left ventricular ejection fraction was 60%, and 52.6% of patients had nonclinically significant cardiovascular disease. Median T-DM1 treatment duration was 5.0 months (range, 0-29 months; median follow-up, 5.9 months), with 18.6% having received more than 18 cycles. The most common any-grade adverse events were fatigue (50.7%) and nausea (38.1%). Adverse events of grade 3 or greater were reported in 46.5%, most commonly thrombocytopenia and platelet count decrease (10.2%). Bleeding of grade 3 or greater was reported in 4 patients (1.9%). Cardiac dysfunction (primarily asymptomatic left ventricular ejection fraction decreases) was reported in 14 patients (6.5%). Among those with measurable disease at baseline (n = 172), objective response rate was 25.6% (95% confidence interval, 19.2%-32.8%).DiscussionThe safety profile of T-DM1 in this real-world setting of heterogeneous, HER2-positive, pretreated, locally advanced breast cancer or MBC was comparable with that reported in phases II and III studies of similar patient populations. T-DM1 was efficacious with no new safety signals.

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