What’s T-DM1 and What’s it For?

15 March, 2020
18-20% of metastatic breast cancers are HER-2+. In other words, they have an overexpression of the HER2 oncogene. Experts developed a new drug called T-DM1 for these types of tumors. In this article, learn all about it.
 

T-DM1 is a new, unique, and selective antibody drug conjugate approved by the European Medicines Agency (EMA) for the treatment of advanced HER2-positive breast cancer. HER2 is the protein “epidermal growth factor receptor 2” that favors the growth of cancer cells. You can find it on the market as Kadcyla.

T-DM1 is made up of two compounds. The first is the known drug trastuzumab, which is an anti-HER2 antibody. The other component is a cytotoxic antimicrotubule molecule: DM1. Cytotoxic antimicrotubule refers to its ability to block the synthesis of microtubules in cell division, a mechanism we’ll discuss below in more detail.

The efficacy of T-DM1

A woman taking pills.

18-20% of metastatic breast cancers are HER2-positive. In other words, they have an overexpression of the HER2 oncogene. Before the development of specific anti-HER2 therapies, the prognosis of patients with HER2-positive tumors was significantly worse than the rest. An oncogene is a gene that, due to its ability to induce mutation or transformation, leads to the formation of cancer in a cell.

 

However, with the development of trastuzumab, approved in 2000, the poor prognosis of HER2-positive breast cancer compared with HER2-negative was counteracted. In 2014, a second anti-HER2 drug was marketed: pertuzumab. The latter drug further extends overall survival in the first-line treatment of advanced HER2-positive breast cancer.

The second line treatment of advanced HER2-positive breast cancer was the only one who was approved to date, which is a combination of chemotherapy with capecitabine plus lapatinib, a tyrosine kinase inhibitor of HER2/EGFR.

A registry study called EMILIA compared treatment with T-DM1 versus treatment with lapatinib plus capecitabine in patients with this type of breast cancer that had been previously treated with trastuzumab and a taxane. The results of this study showed an increase in progression-free survival, an increase in overall survival, and a profile of better tolerated side effects and a significant delay of symptoms until progression to treatment with T-DM1.

 

How T-DM1 exerts its effect on the body

As we mentioned above, T-DM1 is the combination of two drugs: trastuzumab and DM1. T-DM1 combines the mechanisms of action of these two drugs:

  • Like trastuzumab, T-DM1 is able to bind HER2 and block the growth of tumor cells that overexpress this growth factor.
  • Also, it presents the mechanism of action of DM1, which is why it’s able to bind to tubulin.

As it inhibits tubulin, it doesn’t allow the cancer cells to divide, which ultimately causes cell death by apoptosis. The results of in vitro cytotoxicity assays show that DM1 is between 20 and 200 times more powerful than vinca taxanes and alkaloids.

You may also want to read: Breast Cancer: The Different Types, Symptoms and Treatment

The side effects of T-DM1

A woman with breast cancer.

Side effects are the undesirable and unintended events that a patient can expect when they start treatment with a drug.

 

In this regard, the most-reported side effects are nausea, fatigue, and headache. ≥25% of patients suffered from them. So, experts evaluated the safety of T-DM1 in a total of 1871 patients with breast cancer in different clinical trials. They discovered that the most common serious reactions were:

  • Hemorrhages
  • Dyspnea
  • Pain in the bones and muscles
  • Abdominal pain
  • Thrombocytopenia
  • And, finally, vomiting.

You may also want to read: Cryoablation: A New Treatment Option for Breast Cancer

Conclusion

The data reported by studies show that T-DM1 is a very important advance in the treatment of advanced HER2-positive breast cancer. It produces a survival improvement in patients who previously took trastuzumab.

However, despite these advances, HER2-positive cancer is still incurable. Thus, it’s necessary to find new, better-tolerated, and more effective treatments. Therefore, it’s essential to continue actively researching breast cancer.

 
  • Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., … Blackwell, K. (2012). Trastuzumab emtansine for HER2-positive advanced breast cancer. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1209124
  • Barok, M., Joensuu, H., & Isola, J. (2014). Trastuzumab emtansine: Mechanisms of action and drug resistance. Breast Cancer Research. https://doi.org/10.1186/bcr3621
  • Junttila, T. T., Li, G., Parsons, K., Phillips, G. L., & Sliwkowski, M. X. (2011). Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Research and Treatment. https://doi.org/10.1007/s10549-010-1090-x