Why Is T-DM1 Better For Advanced HER2-Positive Breast Cancer Than Standard Medicines?
I have been wondering about the secret of TDM-1’s success. Why is the antibody-drug conjugate able to do a better job? EMILIA trial showed that women with advanced metastatic breast cancer, who had stopped responding to standard therapies lived without progression of their cancer when they were administered TDM1 as compared to women on targeted therapy. Women in the trial are being monitored to check overall survival rate. Click here for more details of EMILIA trial.
In a second trial, MARIANNE, TDM1 is being evaluated for its effect as first targeted therapy treatment for women with advanced-stage HER positive breast cancer. A third trial, TH3RESA study is investigating whether TDM-1 is effective against advanced HER-2 positive breast cancer that has stopped responding to Herceptin and Tykerb.
Now, TDM1 is a combination of Herceptin/Trastuzumab and Emtansine, a cytotoxic agent. The emtansine is attached to the Herceptin. Emtansine is a derivative of maytansine.
HER2 positive cancer cells produce too much of the HER2 proteins and these coat the surface of cancer cells. Herceptin is an FDA approved drug, used to treat HER 2 positive breast cancer and lower recurrence risk. Herceptin attaches itself to the HER2 proteins and disrupt the signaling pathway of growth and progression of cancer.
Emtansine is a chemotherapeutic agent that can disrupt the growth process of any cell. They are not specific to cancer cells and do not retain the ability to recognize them either. Emtansine can affect healthy cells too in a similar manner.
This is where the antibody-drug conjugate gains over standard medications. We have Herceptin which recognizes HER2 proteins and we have a potent killer – the emtansine. The Herceptin linked to the drug is a lethal weapon as far as cancer cells are concerned. Emtansine is transported to the cancer cell where it is released to kill the tumor cell without harming nearby healthy cells.
It would be wrong to say that T-DM1 has no side effects. Unfortunately, any cancer treatment would have some side effects and TDM1 was no different. EMILIA study participants had severe side effects. However, only 41% of TDM1 group experienced severe side effects while 57% of women in standard medication group had them.
TDM-1 is definitely a boon for women with metastatic HER2 positive breast cancer. Antibody-drug conjugates are the current hot topic in medical research and hopefully we can get more of these for other cancers too.