Safety Considerations and Patient-Reported Outcomes of TKIs in HER2-Mutant NSCLC

This episode examines the safety considerations and patient-reported outcomes associated with tyrosine kinase inhibitors (TKIs) in HER2-mutant non-small cell lung cancer (NSCLC). The discussion addresses common adverse effects of TKIs, such as diarrhea, rash, and nail changes, with sevabertinib demonstrating higher rates of rash and gastrointestinal toxicity compared to zongertinib. The panel contrasts these toxicity profiles with those of antibody-drug conjugates (ADCs), emphasizing that ADCs more frequently cause chemotherapy-like side effects, including cytopenias, nausea, fatigue, and notably, interstitial lung disease (ILD)—the latter being less commonly reported with TKIs. The impact of underlying conditions, such as pre-existing lung disease or immunotherapy-related toxicities, is highlighted as a key factor in therapy selection. The importance of patient-reported outcomes, including symptom improvement and quality of life, is underscored, reinforcing that both clinical safety data and individual patient experiences must guide optimal treatment choices for HER2-mutant NSCLC.