Mechanistic Role of Emerging Tyrosine Kinase Inhibitors (TKIs) in HER2-Mutant NSCLC

EP: 1.Value of Comprehensive Molecular Testing in NSCLC

EP: 2.Unmet Needs in HER2-Mutant NSCLC

EP: 3.Treatment of HER2-Mutant NSCLC: Consequences of Delays and Strategies to Improve Timely Initiation

EP: 4.Overview of HER2-Targeted Therapies in NSCLC

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EP: 5.Mechanistic Role of Emerging Tyrosine Kinase Inhibitors (TKIs) in HER2-Mutant NSCLC

EP: 6.Efficacy and Safety of Zongertinib in Previously Treated and Treatment-Naïve HER2-Mutant NSCLC from Beamion LUNG-1 Trial

This episode explores the mechanistic differences and clinical roles of emerging tyrosine kinase inhibitors (TKIs) in the management of HER2-mutant non-small cell lung cancer (NSCLC). The discussion compares zongertinib, a selective HER2-targeting TKI, with sevabertinib, which inhibits both HER2 and EGFR, resulting in distinct side effect profiles—such as increased gastrointestinal symptoms attributed to EGFR inhibition. Both agents have demonstrated significant objective response rates in the second-line setting. The panel contrasts TKIs with antibody-drug conjugates (ADCs), noting that while TKIs generally have a more favorable toxicity profile, ADCs are uniquely approved for both HER2-mutant and HER2 protein-overexpressing tumors, thereby expanding patient eligibility for targeted treatment. Additional considerations include the impact of individual drug toxicity, patient characteristics such as concurrent lung conditions, and the need for ongoing clinical evaluation as these new therapies reshape treatment sequencing and options in HER2-mutant NSCLC.