The role of Trastuzumab Emtansine as a novel-targeted therapy for HER2+ breast cancer: A systematic review

Trastuzumab is the first humanized monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2), tyrosine kinase receptor, that has displayed excellent clinical activity in HER2-overexpressing breast cancer. Despite this, the majority of patients with metastatic HER2-positive breast cancer who initially demonstrate good clinical responses to trastuzumab within the first year of initiation of treatment start to develop resistance within 1 year of initiation of treatment. Even patients on trastuzumab-based chemotherapy regimens have been shown to progress within 1 year of therapy. The antibody-drug conjugate trastuzumab-DM1 (T-DM1) was designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent antimicrotubule agent, DM1 (N-methyl-N-[3-mercapto-1-oxopropyl]-l-alanine ester of maytansinol), a maytansine derivative, to HER2-positive breast cancer cells. Phase I and II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in HER2-positive metastatic breast cancer patients. The EMILIA study, a randomized phase III trial, has shown that T-DM1 provided objective tumor responses and significantly improved progression free survival and overall survival compared to lapatinib and capecitabine combination in HER2-positive metastatic breast cancer patients treated with a prior taxane and trastuzumab regimen. Based on these results, T-DM1 has been indicated in the management of patients with advanced and early stage HER2-positive breast cancer. In this review, we summarize evidence from clinical studies and aim to discuss the potential clinical and therapeutic implications of T-DM1 therapy in the management of HER2-positive breast cancer.