Les anticorps conjugués en oncologie : du concept au trastuzumab emtansine (T-DM1)

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Abstract
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) which associates the selective intracellular targeting of the cytotoxic agent, DM1 (maytansine derivative) to the antitumor activity of trastuzumab. T-DM1 targets the epidermal growth factor receptor 2 (HER2), highly expressed in the most aggressive forms of breast cancer. Current standard of care in HER2-positive advanced or metastatic breast cancers has its limitations, particularly after progression on HER2-targeted approved therapies. T-DM1 showed a significant antitumor activity in vitro and in vivo, and in experimental models resistant to HER2-targeted agents. Phase I and II studies showed that the maximum tolerated dose for T-DM1 is 3.6 mg/kg given intravenously every three weeks. At this recommended dose, T-DM1 provided objective tumor responses and favourable safety profile. A phase II randomised study, evaluating T-DM1 in first line vs trastuzumab plus docetaxel, the current standard of care in advanced or metastatic breast cancers, showed improved tolerability and efficacy. Recently, the results of EMILIA, a phase III randomised study assessing, after prior treatment with trastuzumab and a taxane, the efficacy and the safety of T-DM1 vs lapatinib plus capecitabine, confirmed the therapeutic benefit. T-DM1 appears to be an effective therapeutic option to treat patients with HER2-positive metastatic breast cancer.

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