Trastuzumab emtansine - CAS 1018448-65-1 Catalog number: BADC-00023

In Vitro

In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11-18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11-18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11-18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations.

In Vivo

Trastuzumab emtansine (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.