What Is The T-DM1 And What Is It For?

T-DM1 is a new, unique and selective antineoplastic drug approved by the EMA for the treatment of HER-2 positive advanced breast cancer. HER-2 is a protein known as ‘ epidermal growth factor receptor 2 ‘ that promotes the growth of cancer cells. It is marketed under the name Kadcyla .

T-DM1 is made up of two compounds: one is the well-known drug trastuzumab, which is an anti-HER2 antibody, and the other component is an antimicrotubule cytotoxic molecule – DM1. The fact that it is cytotoxic antimicrotubules refers to its ability to block the synthesis of microtubules in cell division, a mechanism that we will see in more detail later.

Efficacy of T-DM1

18-20% of metastatic breast cancers are HER-2 +, that is, they are characterized by overexpression and / or amplification of the HER2 oncogene. Before the development of specific anti-HER2 therapies, the prognosis of patients with HER-2 + tumors were significantly worse than the rest. An oncogene is a gene that, due to its capacity for mutation or transformation, induces the formation of cancer in a cell.

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

As for second-line treatment of HER2 + advanced breast cancer, the only one approved to date was the combination of chemotherapy with capecitabine plus lapatinib – a HER2 / ERGFR tyrosine kinase inhibitor.

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

Mechanism of action: how does T-DM1 have an effect on the body?

As we have mentioned, T-DM1 is formed by 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 to HER2 and block the growth of tumor cells that overexpress this growth factor.
• It also has the mechanism of action of DM1, which is why it is capable of binding to tubulin.

By inhibiting tubulin it prevents the cancer cell from dividing, which ultimately causes cell death by apoptosis. The results of in vitro cytotoxicity tests show that DM1 is between 20 and 200 times more potent than taxanes and vinca alkaloids.

Adverse reactions of T-DM1

Adverse drug reactions are all those unwanted and unintended effects that occur in an expected way with treatment with a drug.

The most commonly reported side effects were nausea, fatigue, and headache. They were suffered by ≥25% of the patients. In this sense, the safety of T-DM1 was evaluated in a total of 1871 patients with breast cancer in different clinical trials and it was observed that the most frequent serious reactions were:

• Hemorrhage.
• Dyspnoea.
• Pain in the bones and muscles.
• Abdominal pain.
• Thrombocytopenia
• Vomiting

Conclution

The data reported by the studies show that T-DM1 is a very relevant advance in the treatment of advanced HER2 + breast cancer. It produces an improvement in survival in patients previously treated with trastuzumab.

However, despite these advances, HER2 + metastatic disease remains incurable and new, more effective and better tolerated therapies need to be found. Therefore, it is essential to continue active research in breast cancer.