Kadcyla (ado-trastuzumab emtansine) was recently approved for the treatment of breast cancer. It is targeted against HER2. HER2, a protein which drives normal cell growth, is found in different cancer types, including breast cancers. Kadcyla is a compound drug. Kadcyla, previously called T-DM1, is trastuzumab connected to a drug called DM1 that interferes with cancer cell growth.
The approval was based on the EMILIA study. The EMILIA study involving 991 patients who were randomly assigned into two groups:
The Kadcyla group
The lapatinib plus capecitabine group (capecitabine is also a chemotherapy drug)
The trial results showed that:
Those in the Kadcyla group survived progression-free for 9.6 months whereas those in the lapatinib plus capecitabine group survived 6.4 months progression-free. Patients in the Kadcyla group had a median overall survival of 30.9 months while In the lapatinib plus capecitabine group, median overall survival was 25.1 months.
Because the HER2 receptor is expressed so widely in other cancers and not only breast, the temptation is to use it whenever HER expression is found. However, all recommendations to use a drug outside of its indication should be based on clinical studies. It is not an innocuous drug, and gastrointestinal effects, such as vomiting, diarrhea, and stomatitis, were more common than with lapatinib/capecitabine. Kadcyla carries black box warnings for liver toxicity, heart damage (reduction in left ventricular ejection fraction), and fetal harm if given to pregnant women.
However, in the most recent trial, Kadcyla dissapointed.
Results of the anticipated phase III MARIANNE trial found that HER2-positive metastatic breast cancer patients treated with ado-trastuzumab emtansine (T-DM1) plus pertuzumab had similar progression-free survival (PFS) compared with those treated with trastuzumab plus a taxane-based chemotherapy.
Though the trial met its noninferiority endpoint, showing a similar PFS in the first-line setting between the two combination therapies along with T-DM1 alone, it failed to demonstrate that T-DM1 performs better than trastuzumab plus chemotherapy.
The study has been anticipated by clinicians as two of the treatment arms do not include a taxane, which often causes patients to lose their hair, among other toxicities. The full results of the study will be presented at a future medical meeting.
The trial randomized 1,095 patients 1:1:1 to three treatment arms. The primary endpoint was PFS. Secondary endpoints included overall survival, response rate, and the incidence of adverse events. Each of the T-DM1 treatment arms—either with placebo or pertuzumab—were compared with trastuzumab plus either docetaxel or paclitaxel.
Sara Hurvitz, MD, of the UC
- See more at: http://www.cancernetwork.com/her2-positive-breast-cancer/t-dm1-trial-disappoints-her2-positive-breast-cancer#sthash.tJGwZRuU.dpuf
One question remains: When they came up with this name, did they think of Godzila? Does size matter?
Gianni L, et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. N Engl J Med. 2012; 367(19):1783-91.
Niculescu-Duvaz I (June 2010). “Trastuzumab emtansine, an antibody-drug conjugate for the treatment of HER2+ metastatic breast cancer”. Curr. Opin. Mol. Ther. 12 (3): 35060.
Kadcyla, Prescribing Information, 2015
For Lay version see here