Understanding HER2 Alterations in Non–Small Cell Lung Cancer

In this episode, Dr Julia Rotow provides an essential overview of the evolving landscape of HER2 alterations in non–small cell lung cancer (NSCLC). She explains the distinctions between HER2-activating mutations and HER2 overexpression detected via immunohistochemistry (IHC). Because these biomarkers represent separate disease subsets with different therapeutic implications, Dr Rotow highlights the need for complementary genomic and protein-level testing in routine practice. She reviews how HER2-directed antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) have expanded available treatment options in the previously treated setting and discusses why clinicians increasingly need to identify HER2 status early in the diagnostic workup. This episode sets the stage for subsequent case-based discussions focused on real-world treatment selection, sequencing considerations, and the integration of recent clinical trial findings into patient care for HER2-altered NSCLC.