HER2-Mutant NSCLC: Trastuzumab Deruxtecan in Previously Treated

In this segment of the OncLive Peer Exchange®, Dr. Benjamin P. Levy, Dr. Julia Rotow, and Dr. Narjust Florez discuss the clinical evidence supporting trastuzumab deruxtecan (T-DXd) for previously treated HER2-mutant non-small cell lung cancer (NSCLC). Dr. Levy reviews findings from the DESTINY-Lung01 and DESTINY-Lung02 studies, highlighting response rates and the reduction in interstitial lung disease (ILD) rates observed with the 5.4 mg/kg dose in DESTINY-Lung02. Dr. Rotow explains how T-DXd established a standard of care in the second-line setting for patients with HER2-mutant NSCLC who previously had limited targeted treatment options. Dr. Florez emphasizes proactive toxicity management, including antiemetic prophylaxis, counseling about alopecia and other chemotherapy-related adverse effects, monitoring for ILD and cardiac dysfunction, and obtaining baseline echocardiograms. The panel also discusses the importance of recognizing and grading ILD appropriately, including treatment interruption and discontinuation requirements, as clinicians consider treatment sequencing and the evolving role of T-DXd in earlier lines of therapy.