T-DM1 is effective in heavily pretreated patients with metastatic HER2-positive breast cancer.
Major finding: T-DM1 is effective in heavily pretreated patients with metastatic HER2-positive breast cancer.
Approach: A phase II study tested the efficacy of T-DM1 in heavily pretreated patients.
Impact: An antibody–drug conjugate may be useful for treatment of advanced HER2-positive breast cancer.
The prognosis of patients with human epidermal growth factor receptor 2 (HER2) gene-amplified breast cancer has improved with the development of the HER2 monoclonal antibody trastuzumab and the HER1/HER2 tyrosine kinase inhibitor lapatinib. However, despite the success of these targeted therapies, HER2-positive breast cancers often progress, leaving patients with few treatment options. Trastuzumab emtansine (T-DM1), an antibody–drug conjugate that delivers the potent antimicrotubule agent derivative of maytansine 1 (DM1) to HER2-expressing cells, has been shown to exhibit antitumor activity in patients with HER2-positive breast cancer. To investigate whether T-DM1 is active in patients with treatment-refractory metastatic HER2-positive breast cancer, Krop and colleagues tested its efficacy in 110 patients whose disease had progressed on all standard HER2-directed therapies as well as a taxane, an anthracycline, and capecitabine. In this single-arm, phase II study, treatment with T-DM1 was well tolerated and resulted in an overall response rate of 34.5% and a median progression-free survival duration of 6.9 months. Interestingly, patients with confirmed HER2-positive primary tumors had an overall response rate of 41.3%, compared with 20% in patients with HER2-normal tumors, suggesting that HER2 status of a tumor may change over time and that even clinically undetectable levels of HER2 may be sufficient to render a tumor sensitive to T-DM1. Given that this cohort of patients had received a median of 7 prior treatments for metastatic breast cancer, these findings indicate that T-DM1 may represent a therapeutic option for refractory HER2-positive disease. Future studies are needed to further elucidate a role for antibody–drug conjugates in breast cancer.
Krop IE, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, et al. 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. J Clin Oncol 2012 May 29 [Epub ahead of print].
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