Results from the international EMILIA study suggest a new effective treatment for HER2 positive metastatic breast cancer, using trastuzumab (Herceptin) linked with the potent chemotherapy DM1.
The study, first presented at the June 2012 American Society of Clinical Oncology (ASCO) meeting, suggests trastuzumab emtansine, or T-DM1, not only targets cancer cells directly, but also decreases the chance of or delays some side effects.
Compared to standard therapy, T-DM1 showed an increase in progression-free survival, the time during and after treatment the cancer remains stable. In an Oct.1 news release, Genentech, the maker of trastuzumab and T-DM1, announced updated survival results from the study. These results showed that people with HER2 positive metastatic breast cancer treated with T-DM1 also had a significantly longer rate of overall survival, the time a person lives from research study participation until death from any cause.
Background and Reason for the Study
Standard treatment for HER2 positive metastatic breast cancer that grows despite trastuzumab treatment is lapatinib (Tykerb) plus capecitabine (Xeloda), a chemotherapy medicine.
Like all chemotherapy, capecitabine damages not only cancer cells but also healthy tissue, causing side effects such as nausea, vomiting and fatigue, as well as redness, swelling and blistering on the hands and feet (hand-foot syndrome). Treatment doses are sometimes reduced to manage side effects, which could make therapy less effective.
T-DM1 is the first antibody-drug conjugate to be studied on a large scale. A burgeoning area in cancer research, antibody-drug conjugates pair chemotherapy with targeted medicine to deliver chemotherapy’s powerful effects directly to the tumor while sparing healthy cells from its toxic effects. Without trastuzumab, DM1 results in such difficult side effects that it was not considered a viable treatment until this study.
Study Structure
EMILIA consisted of 978 participants whose HER2 positive metastatic breast cancers no longer responded to trastuzumab. Participants were randomly assigned to receive T-DM1 every three weeks, or the standard regimen of capecitabine and lapatinib, called XL, twice daily for 14 days every three weeks.
Participants received treatment until side effects were no longer tolerable or the cancer stopped responding to treatment. Researchers followed participants an average of 12 months.
Findings
Progression-free survival improved from 6.4 to 9.6 months for women assigned T-DM1, a 35 percent reduction in the risk of progression.
Data suggest an overall survival benefit with T-DM1. After two years, 65.4 percent of participants on the regimen were alive, compared to 47.5 percent of those treated with XL. When the study's findings were initially presented at the ASCO meeting, investigators said participants needed to be followed longer to determine whether these findings would reach statistical significance, meaning the differences are unlikely to have happened by chance. Genentech confirmed the results as statistically significant in an Aug. 26 news release. Updated results, presented on Oct. 1, 2012 at the European Society for Medical Oncology (ESMO) Congress and published in the online edition of the New England Journal of Medicine, showed that risk of death was reduced by 32 percent for participants treated with T-DM1 compared to those who received standard treatment. On average, EMILIA study participants receiving T-DM1 survived 5.8 months longer than those who received XL; the median overall survival for T-DM1 was 30.9 months and 25.1 months for participants treated with XL.
Overall, those who received T-DM1 had fewer side effects that would prompt a change in treatment dose. For 41 percent of T-DM1 participants, side effects included effects on liver function and low platelet counts, which help with blood clotting. In the XL group, 57 percent of participants had redness and blistering on the hands and feet, diarrhea, nausea and vomiting.
Commenting on the study, Chau Dang, MD, of Memorial Sloan-Kettering Cancer Center in New York, told LBBC the treatment’s relation to side effects “is a win-win” for women.
“So often, the ‘more effective’ treatment than its comparator becomes unappealing due to its unacceptable toxicities, but this is not the case for T-DM1,” Dr. Dang says. “Time to symptom progression was longer with T-DM1.”
What This Means for You
Many providers consider EMILIA’s findings a breakthrough in HER2 positive metastatic breast cancer, especially for women whose cancers fail to respond to first- or second-line treatment. Dr. Dang says forthcoming results from another trial, the MARIANNE study, will evaluate T-DM1 as an initial treatment.
Genentech says it plans to apply for FDA approval later this year. For now, T-DM1 is available through clinical trials. Based on overall survival results, people in the lapatinib and capecitabine arm of EMILIA will be offered the option to receive T-DM1. Genentech also plans to establish an expanded access program (EAP) in the U.S. to provide T-DM1 under certain circumstances for people living with HER2 positive metastatic breast cancer while the company seeks regulatory approval.
To learn more about the updated findings of the EMILIA study, check out the New England Journal of Medicine’s website.
To learn more about T-DM1, check out Living Beyond Breast Cancer’s June 2012 teleconference. LBBC will monitor news relating to T-DM1, as well as other new studies, and report findings on .
Blackwell K, Miles D, et al: Primary results from EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) vs capecitabine and lapatinib in HER2-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. J Clin Oncol 30, 2012 (suppl; abstr LBA1).
