A phase III randomized study of the investigational agent trastuzumab emtansine (T-DM1) vs. standard therapy using capecitabine and lapatinib found significant and clinically meaningful improvement in progression-free survival (PFS) for T-DM1 in women with HER2-positive locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab.  Results were presented at the American Society of Clinical Oncology's 48th Annual Meeting.

T-DM1 is an experimental antibody-drug conjugate that consists of the antibody trastuzumab linked to the cytotoxic drug emtansine (DM1).

"The drug worked. It was significantly better than a very effective approved therapy for HER2 overexpressing metastatic breast cancer," said lead study author Kimberly L. Blackwell, M.D., professor of medicine and assistant professor of radiation oncology at Duke Cancer Institute at Duke University. "Also, as a clinician who takes care of a lot of breast cancer patients, I'm pleased that this drug has very little dose-limiting toxicity. Patients don't lose their hair from this drug. For patients facing metastatic breast cancer, this is a breakthrough."

The international study, called EMILIA, randomized nearly 1,000 patients to receive either T-DM1 or XL every three weeks until their disease progressed or they experienced unmanageable toxicity.

The median PFS for patients receiving T-DM1 was 9.6 months, compared to 6.4 months in the group receiving capecitabine and lapatinib (a regimen known as XL) – a difference that was statistically significant.

After two years, 65.4 percent of the T-DM1 patients were alive, compared to 47.5 percent of the XL patients. This difference in statistical significance did not meet the trial's predetermined statistical survival threshold for the first analysis. The second survival analysis planned for later in the study will provide additional information.

The most common adverse events of Grade 3 or above for T-DM1 included thrombocytopenia (12.9 percent vs. 0.2 percent) and elevation in liver function tests. These side effects resolved when patients took a break from the drug, Dr. Blackwell said. Dose reductions were greater for patients in the XL group: 53.4 percent for capecitabine, 27.3 percent for lapatinib, and 16.3 percent for T-DM1.

Patients in the XL group experienced more diarrhea (20.7 percent vs. 1.6 percent), hand-foot syndrome (16.4 percent vs. 0), and vomiting (4.5 percent vs. 0.8 percent).