Emerging treatment strategies for HER2-mutant NSCLC: Striving for selectivity, efficacy, and tolerability

Abstract

Human epidermal growth factor receptor 2 (HER2) has been identified as a distinct molecular drug target in patients with non-small cell lung cancer (NSCLC), with mutations detected in approximately 1.8–5.6% of tumors. While HER2-directed agents have revolutionized treatment algorithms in breast and gastric cancers, there remains an unmet need for patients with HER2-mutant NSCLC. Currently, no first-line HER2-directed agents are available and, until recently, trastuzumab deruxtecan, a HER2-targeting antibody–drug conjugate, was the only approved HER2-directed treatment option in the previously treated setting. In the current review, we summarize the development of treatment options for HER2-mutant NSCLC, including antibody–drug conjugates and tyrosine kinase inhibitors.