Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer
Cet article passe en revue les travaux récents sur le trastuzumab emtasine pour le traitement des patientes atteintes d'un cancer métastatique du sein HER2+
Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent anti-microtubule agent DM1, linked via a non-cleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive tumor cell combined with trastuzumab's activation of antibody-dependent cellular cytotoxicity and inhibition of HER2 mediated signal transduction. In phase 2 studies, T-DM1was active in patients with trastuzumab and lapatinib refractory metastatic breast cancer (MBC) and led to improved progression-free survival compared to the combination of trastuzumab and docetaxel in the first line setting. In a recent phase 3 trial in patients with MBC who previously received trastuzumab and a taxane, T-DM1 resulted in improved progression-free and overall survival compared to capecitabine and lapatinib. T-DM1 is associated with a favorable toxicity profile; reversible thrombocytopenia and hepatic transaminase elevations are the only grade >3 adverse event present in ≥5% of patients. Alopecia, peripheral neuropathy, and neutropenia are distinctly uncommon. Based on its improved efficacy and toxicity compared to capecitabine/lapatinib, T-DM1 should be considered the standard for patients with HER2+ MBC who have previously progressed on trastuzumab. Results from additional randomized studies in MBC are pending, and trials in the (neo)adjuvant setting are being initiated.