Ado-trastuzumab emtansine (Kadcyla)

A HER2 targeted antibody conjugate for the treatment of HER2 positive late stage breast cancer.

A combination of an HER2 targeted antibody, trastuzumab and T-DM1, a microtubule inhibitor.

Trastuzumab emtansine (T-DM1)

Antitubulin agent chemically linked to trastuzumab

An antibody-drug conjugate that incorporates the HER2 targeted antitumor properties of trastuzumab with the cytotoxic activities of the microtubule-inhibitory agent DM1, derivative of maytansine.

Tradename Kadcyla.

The antibody and the cytotoxic agent or conjugated by a stable linker.

T-DM1 allows intracellular drug delivery to HER2 overexpressing cells, improving the therapeutic index and minimizing exposure to normal tissues.

Phase 2 studies have shown clinical activity of T-DM1 in patients with HER2 positive advanced breast cancer.

The EMILIA study, a phase 3 trial assessed the efficacy of T-DM1as compared with lapatinib plus capecitabine in patients with HER 2 positive advanced breast cancer previously treated with trastuzumab and a taxane:T-DM1 significantly prolonged progression free and overall survival with less toxicity than the lapatinib plus capecitabine arm(EMILIA Study group, Verma S et al).

Indicated as a single agent for the treatment of HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.

Administered intravenously every 3 weeks.

In a phase 3 study of 991 patient with HER2 positive locally advanced breast cancer for metastatic breast cancer with failed trastuzumab and a taxane treatment: median progression free survival 9.6 months compared with 6.4 months in patients treated with lapatinib + capecitabine, with the median survival of 30.9 months versus 25.1 months.

The most common side effects were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, constipation, and increased transaminases, and sensory neuropathy.

Has mainly reversible toxic effects.

GATSBY study of trastuzumab emtansine in advanced HER2 positive gastro esophageal cancer progressing on a platinum and a fluoropyrimidine had a 20% objective response rate.

KATHERINE trial randomized HER2 positive patients with significant residual cancer burden after neoadjuvant HER2 therapy to either trastuzumab or T-DM1out to a year of total therapy.: T-DM1 improved invasive disease free survival by 11.3% at a median of 41 months follow up.

Neoadjuvant combination of trastuzumab, pertuzamab, and docetaxel is equal to trastuzumab  emtansine monotherapy in HER positive breast cancer.

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