Emerging strategies for the dual inhibition of HER2-positive breast cancer

摘要

Purpose of Review: To review the recently published trials to help us refine and optimize the use of approved HER2-targeted agents (trastuzumab and lapatinib) and highlight future combination strategies for the treatment of HER2-positive breast cancer. Recent Findings: Pertuzumab, which prevents the dimerization of HER2/HER3, and trastuzumab emtansine (T-DM1), a novel antibody drug conjugate (trastuzumab joined via a stable linker to a derivative of the potent cytotoxic agent maytansine), have both demonstrated promising clinical activity in HER2-positive breast cancer. Dual anti-HER2 regimens combining trastuzumab with lapatinib or pertuzumab show remarkable synergy and improved outcomes in patients previously thought to have refractory disease. In the neoadjuvant setting, dual anti-HER2 blockade and chemotherapy have almost doubled the rates of pathologic complete response compared to single anti-HER2 therapy. A better understanding of the mechanisms of resistance has led to the development of rational combination therapies cotargeting the PI3K and vascular endothelial growth factor signaling pathways. Summary: New therapeutic options such as pertuzumab or T-DM1 will yield clinically meaningful improvements for patients with HER2-positive breast cancer. Given the high prevalence of intrinsic and acquired resistance to single-agent regimens, the treatment paradigm is shifting toward a dual anti-HER2 therapeutic approach. ? 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.