Dr. Heymach on the Potential Utility of Afatinib in NRG1 Fusion+ NSCLC

John V. Heymach, MD, PhD, chair, professor, and David Bruton Jr. Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, professor, Department of Cancer Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the potential utility of afatinib (Gilotrif) in NRG1 fusion–positive non–small cell lung cancer (NSCLC).

NRG1 fusions are generated from a protein that includes a ligand for the EGFR receptor, says Heymach. Although the protein is in the EGFR family, the fusion is not driven by EGFR or HER2 activating mutations and is, instead, driven by persistent activity of the ligand, Heymach explains. Moreover, inhibiting HER3 is likely tied to NRG1 fusions because HER2 and HER3 are drivers of the alteration’s activity. Additionally, heregulin can bind to HER4, Heymach says.

As such, agents with a broader spectrum of activity may have clinical utility in NRG1 fusion–positive NSCLC. Afatinib, a pan-ErbB family inhibitor, has shown activity in patients with NRG1 fusion–positive NSCLC and may have utility as a novel treatment option in this patient population. Additionally, HER3-directed monoclonal antibodies are also being evaluated in this space, concludes Heymach.