EGFR-MET Dual Targeting Rationale in HNSCC

Paul L. Swiecicki, MD, of the University of Michigan Rogel Cancer Center, discusses the biological rationale for targeting epidermal growth factor receptor (EGFR) and MET in head and neck squamous cell carcinoma (HNSCC). Dr Swiecicki notes that EGFR is overexpressed in more than 90% of HNSCC tumors, especially HPV-negative disease, and that this overexpression is a known growth driver that led to the approval of cetuximab, both as monotherapy and in combination with platinum and 5-fluorouracil. He explains that EGFR-targeted therapy alone has not been a panacea, with responses that are often limited in depth and duration due to several resistance mechanisms, including activation of the MET pathway. Amivantamab, a bispecific antibody with dual EGFR and MET targeting plus immune cell-directing activity, is designed to address both the growth pathway and this resistance pathway simultaneously, an approach Dr Swiecicki shares that may translate into greater depth and durability of antitumor response.