Case 2: Sequencing HER2-Directed ADCs and TKIs in Complex Clinical Scenarios

This episode addresses treatment selection for a patient with both HER2-mutant and HER2-overexpressing NSCLC, emphasizing how dual biomarkers influence therapeutic decision-making. Dr Julia Rotow describes her approach to balancing available HER2-directed ADCs and TKIs, incorporating factors such as prior pneumonitis, functional status, and patient preferences. She reviews efficacy data for trastuzumab deruxtecan in HER2-mutant NSCLC, including response rates and progression-free survival from previously treated cohorts, and explains how these results support its role in the therapeutic sequence. At the same time, she discusses why HER2 TKIs remain important options for patients with HER2 exon 20 insertions, particularly in settings where clinicians aim to reduce the risk of recurrent pulmonary toxicity.