Opportunities for Positioning TKIs as First-Line Therapy in HER2-Mutant NSCLC

This episode explores the potential to position tyrosine kinase inhibitors (TKIs) as first-line therapy for HER2-mutant non-small cell lung cancer (NSCLC). The discussion reviews current standard first-line treatments, such as chemotherapy and chemoimmunotherapy, which offer limited progression-free survival and modest response rates for this patient subgroup. Panelists outline how ongoing phase 3 trials are directly comparing HER2-targeted TKIs—including zongertinib and sevabertinib—and antibody-drug conjugates against these traditional regimens, with the expectation that positive results could lead to a shift in frontline therapy standards. The conversation emphasizes that, pending supportive trial data, TKIs may offer better tolerability and efficacy than existing options and could rapidly be adopted in practice. There is also reinforcement of the point that immunotherapy alone is not adequate for HER2-mutant NSCLC, highlighting the continuing need for improved approaches. Patient selection and evolving evidence will remain crucial as the treatment landscape advances.