Data from the phase 3 EMILIA trial shows progression-free survival benefit in metastatic HER2-positive breast cancer patients.
The investigational breast cancer drug T-DM1 had a sputtering start when the Food and Drug Administration refused to grant it accelerated approval in 2010, even with promising phase 2 data. As the ASCO headliner this year, though, it appears new data from the large phase 3 trial, called EMILIA, will be enough to gain approval and make it available to metastatic HER2-positive breast cancer patients soon.
T-DM1 is one of a reformulated class of drugs called antibody-drug conjugates. It fuses together the Herceptin antibody (trastuzumab) to a potent drug called emtansine, packing a powerful punch to cancers that are fueled by overexpression of the HER2 receptor—even in patients whose cancers have prog- ressed with Herceptin. Emtansine’s potency is at least 100 times more powerful than paclitaxel, and administration without severe side effects has been a challenge until now. Linking it to Herceptin, which delivers it directly to the cancer cell, reduces those side effects.
In the EMILIA trial, researchers followed 978 women whose cancer had progressed on a taxane and Herceptin. The women were given either an infusion of T-DM1 three times a week or the standard treatment of Xeloda (capecitabine) and Tykerb (lapatinib). After two years, researchers found that women in the investigational arm lived longer without disease progression (9.6 months compared with 6.4 months with standard therapy) and had fewer treatment-related side effects. There also appears to be a survival advantage, but researchers are waiting for data to mature before they can confirm that T-DM1 prolongs life. At the two-year follow-up, 65.4 percent of patients on T-DM1 were alive compared with 47.5 percent on the standard treatment.
"I'd say close to 18 more out of 100 women were alive because they got one drug over another," says Kimberly L. Blackwell, MD, who presented the study at ASCO. "We've never seen that kind of absolute difference in overall survival for a drug that doesn't induce life-altering toxicities. We haven't even seen that amount of survival benefit in highly toxic treatments."
Although the EMILIA trial tested T-DM1 alone, there are clinical trials combining T-DM1 with approved and investigational drugs, including pertuzumab, which was recently granted approval for metastatic breast cancer on June 8. Data from the EMILIA trial will be submitted to the FDA later this year for possible approval in metastatic, HER2-positive breast cancer.