Integrating Evolving HER2 Testing Standards Into Practice

This segment explores how recent updates in HER2 testing guidelines are reshaping treatment selection and clinical workflow. Dr. Riess notes that broad NGS has become standard of care for all patients with metastatic NSCLC, enabling identification of HER2 exon 20 insertion mutations, which now have multiple targeted therapies. He reviews the agents currently approved, such as zongertinib (a HER2-selective TKI) and trastuzumab deruxtecan (T-DXd, an ADC), and discusses emerging data from sevibertinib, which demonstrated promising activity in recent trials.

The experts highlight that while HER2 mutation testing has long been a routine part of NGS panels, HER2 IHC represents a more recent and important update. HER2 IHC 3+ now defines a distinct actionable subset eligible for T-DXd in the second-line setting, offering a clinically meaningful alternative to docetaxel. This broadens the spectrum of patients who may benefit from HER2-directed therapy beyond those with exon 20 insertions.

Dr. Patel describes the strong efficacy signals from ongoing phase I/II trial programs, including objective response rates exceeding 70% for HER2 TKIs in treatment-naive patients. The segment emphasizes the need to understand differences between mutation-driven and expression-driven indications, as well as the importance of reassessment after disease progression to identify newly emerging HER2-related resistance mechanisms.

The rapid pace of testing and therapeutic advancements requires clinicians to remain vigilant in updating their workflows to ensure appropriate identification of all clinically actionable HER2 aberrations.