EMILIA study suggests new therapy superior to the combination of lapatinib and capecitabine
Updated results from the international EMILIA study show that trastuzumab emtansine (T-DM1), an antibody-drug conjugate, increased both progression-free and overall survival in people with HER2 positive locally advanced and metastatic breast cancer. The new findings also confirm that T-DM1 offers a less toxic treatment option than a standard combination of lapatinib (Tykerb) plus capecitabine (Xeloda), called XL.
Progression-free survival measures the time during and after treatment that cancer does not grow and includes events, such as deaths, that could reflect disease progression, even if not documented in the trial. Overall survival is the time from beginning the study until death from any cause. These two endpoints (trial goals) are related and often associated, but improved overall survival is usually considered the best possible evidence that one treatment is superior to another.
Background and Reason for the Study
EMILIA, launched in 2009, compared T-DM1 to XL, a standard therapy for HER2 positive metastatic breast cancer that grows despite treatment with trastuzumab (Herceptin).
XL is an effective treatment and FDA-approved for cancers that worsen despite treatment with trastuzumab and a taxane, but the impact of capecitabine on healthy cells can cause side effects that may require lowering the dose.
Antibody-drug conjugates like T-DM1 work by delivering chemotherapy directly into cancer cells. The medicine attaches to an antibody, which targets proteins on the surface of the cancer cell. In T-DM1, the anti-HER2 antibody trastuzumab (T) binds with the dissolvable linker MCC to mertansine (DM1), a potent chemotherapy. Together, the MCC and DM1 is called emtansine. After T-DM1 is inside the cell, the link (MCC) between mertansine and the trastuzumab breaks or dissolves, and the DMT1 is free to interrupt the growth of cancer cells, killing them from within. Treating cancer cells this way may protect healthy cells from the damage done by standard chemotherapy.
Structure of the Study
EMILIA enrolled 991 people with HER2 positive locally advanced or metastatic breast cancer whose cancers progressed after treatment with trastuzumab and a taxane. Participants were randomly assigned to T-DM1, given by vein every three weeks, or to lapatinib plus capecitabine, taken as a pill twice daily for 14 days every three weeks.
Participants had to be in good heart health, and were excluded if they had prior treatment with any of the medicines under study, had prior severe neuropathy (nerve damage), had symptoms of or treatment for brain metastases, or had a history of heart problems.
Researchers assessed tumors every six weeks until the cancer grew, and six weeks after progression. They closely monitored heart function and side effects.
T-DM1 provided longer progression-free and overall survival than XL, as well as less severe and less frequent side effects. As reported in June at the American Society of Clinical Oncology annual meeting, median progression-free survival was 3.2 months longer with T-DM1, increasing from 6.4 months with XL to 9.6 months with T-DM1.
In this second analysis, overall survival increased by nearly six months with T-DM1, from a median of 25.1 months to 30.9 months. Participants in the T-DM1 arm experienced fewer, less severe side effects than their peers in the XL arm, who also needed more dose reductions to manage those side effects. Fewer participants in the T-DM1 arm had to stop treatment because of side effects than in the other group – 7.6 percent versus 9.4 percent.
The most common side effect of T-DM1 was a low blood platelet count, reported in about 13 percent of participants. Platelets help to clot blood. Most participants were able to continue treatment after the dose was reduced. About 4 percent of TDM-1 recipients had trouble with liver function, but after dose reduction could continue treatment.
What This Means for You
The improvement in overall survival and low rate of severe side effects presented in this study show that T-DM1 has the potential to become an effective, less toxic line of treatment for HER2 positive metastatic breast cancer. The findings also suggest that antibody-drug conjugates like T-DM1 may offer an exciting new method of receiving chemotherapy medicine by sparing healthy cells, causing fewer side effects overall.
Genentech/Roche, the maker of T-DM1, announced its plan to submit the medicine for FDA approval in an October 1 news release. TDM-1 is available now in clinical trials. Living Beyond Breast Cancer will continue to report on T-DM1 and other new therapies for HER2 positive breast cancer on lbbc.org.
Verma, Sunil, Miles,David, et al: Trastuzumab Emtansine for HER2 Positive Advanced Breast Cancer. N Engl J Med 2012 Oct 1 [ahead of print].