Anti-HER2 Mechanisms of Approved HER2 Inhibitors

Earn CME for related activities: https://www.naccme.com/oln Patients whose disease progresses or relapses on trastuzumab now have 3 new therapeutic options: lapatinib, pertuzumab, and T-DM1. Each of these agents has a unique mechanism of targeting HER-2 signaling and cross-talk among HER family members. When considering treatment for patients past the first-line setting, the goals of therapy should be to improve survival and minimize treatment-related toxicity. Only T-DM1 has demonstrated survival benefits over other traditional choices, such as lapatinib and capecitabine, and should therefore represent a standard of care for second-line patients. Dual HER2 blockade with lapatinib and trastuzumab also led to a survival advantage over lapatinib alone in more heavily pretreated patients than those enrolled in EMILIA. This combination of HER2- targeting agents also offers a low toxicity profile. Finally, once T-DM1 and lapatinib strategies have been exhausted, continuation of trastuzumab in combination with chemotherapy has proven activity. The increasing number of options in the second-line setting and beyond is good news for patients faced with trastuzumab-refractory metastatic breast cancer