T-DM1 in Breast Cancer: Improves Survival, Awaits Approval

Zosia Chustecka

August 28, 2012

August 28, 2012 — A novel twist on the targeted agent trastuzumab (Herceptin, Genentech/Roche), known as trastuzumab emtansine (or T-DM1), is a step closer to market.

Updated results from a pivotal trial of women with HER2-positive metastatic breast cancer show that the novel product is associated with a significant improvement in overall survival. The new data will be added to the approval application just submitted by Genentech in the United States and about to be submitted by Roche in Europe.

Approval is expected in mid-2013 in the United States and late in 2013 in Europe.

In T-DM1, the HER2-targeted antibody trastuzumab (Herceptin) is chemically linked to cytotoxin mertansine, a lethal poison. The antibody homes in on HER2 breast cancer cells, delivering the chemotherapy directly to the tumor, which reduces the risk for toxicity.

T-DM1 was evaluated in the large pivotal EMILIA trial of women with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab and a taxane-based chemotherapy. These women were randomized to receive treatment with T-DM1 or with another HER2-targeted therapy, lapatinib (Tykerb, GlaxoSmithKline), plus chemotherapy with capecitabine (Xeloda, Roche).

Previous results from this trial showed that T-DM1 significantly improved progression-free survival, compared with the lapatinib/capecitabine combination. These results were presented a few months ago at the annual meeting of the American Society of Clinical Oncology, and were enthusiastically welcomed by breast cancer experts, as reported at that time by Medscape Medical News.

"This is a very different kind of therapy, much better tolerated and more active than some of our existing options for trastuzumab-refractory HER2-positive breast cancer," said Hal Burstein MD, associate professor at Harvard Medical School and medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, at the time.

The original results for overall survival showed a trend toward superiority for T-DM1, but they did not reach statistical significance.

The data have now matured, and the difference in overall survival between T-DM1 and the lapatinib/capecitabine combination is now statistically significant, Genentech announced in a press release. The actual data showing the magnitude of improvement have not been released; it will be presented at an upcoming medical meeting, according to the company.

On the basis of the updated survival results, women in the trial who are taking lapatinib and capecitabine will now be offered crossover to T-DM1. In addition, Genentech plans to open an Expanded Access Program in the United States to provide, under certain circumstances, access to the product while the approval process in underway.

About 25% of all breast cancers are HER2-positive. The current data support the use of T-DM1 only as a second-line treatment in women with HER2-positive metastatic breast cancer who have already received trastuzumab and progressed. However, the companies are conducting another study (known as MARIANNE) to explore its use in the first-line setting.

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