HER2-Mutant NSCLC: T-DXd Toxicity Management and Intracranial Activity

In this segment of the OncLive Peer Exchange®, Dr. Benjamin P. Levy, Dr. Julia Rotow, and Dr. Narjust Florez discuss practical considerations for managing trastuzumab deruxtecan (T-DXd) in patients with HER2-mutant non-small cell lung cancer (NSCLC). Dr. Rotow emphasizes proactive antiemetic management, monitoring for interstitial lung disease (ILD), and educating patients to report symptoms promptly. The panel discusses approaches to managing grade 1 ILD, including treatment interruption until resolution and individualized decisions regarding dose maintenance or reduction. The experts acknowledge that dose modifications and treatment sequencing often require clinical judgment when evidence is limited. The discussion then shifts to the intracranial activity observed with T-DXd in the DESTINY-Lung02 study. Dr. Rotow and Dr. Florez describe clinical experiences with intracranial responses, including durable disease control in selected patients. They consider how these findings may influence decisions about radiation timing, while recognizing that the available evidence remains limited and that treatment decisions must be individualized. The panel highlights the importance of balancing CNS disease control, treatment toxicity, and patient preferences.