TDM1- 2012 update -pro
Trastuzumab emtansine (INN), variously called L trastuzumab-DM1 or trastuzumab-MCC-DM1, or T-DM1 is an antibody-drug conjugate consisting of the antibody trastuzumab (Herceptin) linked to a cytotoxic agent that is a derivative of maytansine (DM1). Is is promising drug and it is in several studies. EMILIA, a phase III trial of 991 people with HER2-positive unresectable locally advanced or metastatic breast cancer, comparing T-DM1 versus capecitabine plus lapatanib in patients previously treated with trastuzumab and a taxane chemotherapy, showed improved progression free survival in patients treated with T-DM1 (median 9.6 vs. 6.4 months) with an improved safety profile.
The study sponsor reported in August 2012 that T-DM1 significantly improved survival. Median progression-free survival, one of the trial’s primary efficacy end points, was 9.6 months with T-DM1, compared with 6.4 months with capecitabine-lapatinib (hazard ratio, 0.65; P less than .0001). Results were largely the same across patient subgroups, except for an apparent lack of benefit among women aged 65 years or older.
There is also the MARIANNE study, which compares taxane (docetaxel or paclitaxel) plus trastuzumab vs T-DM1 vs T-DM1 plus pertuzumab as first-line treatment for people with HER2 positive unresectable locally advanced or metastatic breast cancer and the TH3RESA stud, which is comparing T-DM1 vs treatment of physician’s choice for people with HER2 positive metastatic breast cancer previously treated with trastuzumab and lapatinib.
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): 350–60.
Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87.
See the Lay version here