Dual HER2-Targeting in the Adjuvant Setting: Where We Have Been and Where We Are Going

Adjuvant human epidermal growth factor receptor 2 (HER2)-directed treatment has changed dramatically over the past decade. Historically, the addition of 1 year of trastuzumab to adjuvant chemotherapy has significantly improved both disease-free survival and overall survival across several studies. More recently, and in the metastatic setting, dual HER2-targeted therapy-beyond that of trastuzumab alone, and in combination with monoclonal antibodies such as pertuzumab and tyrosine kinase inhibitors such as lapatinib-has shown a survival benefit. As is common in drug development, promising agents in the metastatic setting are then examined in the curative setting. This article will provide an overview of the efficacy of dual HER2-targeted therapy in the adjuvant setting as reported in the APHINITY, ExteNET, and ALTTO trials. Potential toxicities with dual HER2-targeted therapy and the financial consequences of adding additional HER2-targeted therapy, beyond trastuzumab, in the adjuvant setting will also be discussed.