Case 1: Managing HER2-Mutant NSCLC and ILD

In this case-based episode, Dr Julia Rotow reviews the clinical presentation and treatment course of a 58-year-old woman with metastatic HER2-mutant NSCLC. She discusses frontline decision-making for PD-L1–low adenocarcinoma, emphasizing the guideline-consistent role of platinum-based chemotherapy combined with immunotherapy. The episode then explores second-line management using trastuzumab deruxtecan, which demonstrated a meaningful tumor response but was complicated by symptomatic interstitial lung disease (ILD). Dr Rotow outlines key principles for evaluating, diagnosing, and managing ILD in patients receiving HER2-directed ADCs, including the importance of early recognition, corticosteroid initiation, and permanent treatment discontinuation in the setting of symptomatic toxicity. This scenario illustrates how real-world toxicity events influence sequencing decisions and underscores the need for close monitoring when using ADC-based therapies. The episode concludes by framing the clinical question of how to approach treatment once ADC therapy is stopped for adverse events.