Role of EGFR Monoclonal Antibodies in the Management of Non–small Cell Lung Cancer

Dysregulation of epidermal growth factor receptor (EGFR) signaling due to receptor overexpression or activating mutation is associated with cancer cell proliferation, metastasis, and survival. EGFR has become an important therapeutic target for non–small cell lung cancer (NSCLC), and several EGFR-targeted agents, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs), have been developed. The EGFR-TKIs gefitinib, erlotinib, and afatinib have been approved for the treatment of advanced NSCLC, and sensitivity to these drugs has been shown to be associated with the presence of EGFR mutations. Various mAbs to EGFR have also been evaluated in preclinical and clinical studies. In particular, phase III trials have shown a clinically significant survival benefit for addition of the anti-EGFR mAbs cetuximab or necitumumab to a platinum doublet in chemotherapy-naïve patients with advanced NSCLC. We here summarize the results of completed and ongoing clinical trials of EGFR-targeted mAbs for the treatment of NSCLC.