Role of HER3-DXd in Advanced NSCLC Treatment Landscape

This is a synopsis of an Insights series featuring Ticiana Leal, MD, of Winship Cancer Institute of Emory University, and Sandip P. Patel, MD, of UC San Diego Health Moores Cancer Center.

Associate Professor and Director of the Thoracic Medical Oncology Program at the Winship Cancer Institute of Emory University Ticiana Leal, MD and Professor of Medical Oncology at the University of California, San Diego Sandip P. Patel, MD discussed optimal positioning of the anti-HER3 antibody-drug conjugate patritumab deruxtecan in non–small cell lung cancer (NSCLC) treatment paradigms.

Dr. Patel noted current data supports use after progression on osimertinib or other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), likely in the second line setting initially. Ongoing trials are investigating moving patritumab deruxtecan into earlier lines or combining with osimertinib upfront. Without an enrichment biomarker, widespread application could be supported given response rates around 30% post-TKI.

Dr. Leal agreed the second line space post-osimertinib progression seems the clearest and most near-term fit. In the frontline, the bar is high given the efficacy and toxicity hurdles new combinations must clear. Using patritumab deruxtecan after initial osimertinib therapy could also be reasonable pending additional research.

Both speakers concurred HER3 targeting antibody-drug conjugates address an important unmet need in TKI resistant EGFR mutated NSCLC. While many questions remain regarding optimal timing and patient selection, strong response signals warrant ongoing investigation through rigorously designed clinical trials.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.