Biomarkers for monoclonal antibody targeting EGFR in NSCLC: Challenges, current status, and future perspectives

Targeting EGFR has a long history in the treatment of non-small cell lung cancer (NSCLC). It was around the 2000s that it was reported that EGFR protein expression increased with bronchial dysplasia in high-risk smokers and patients with lung cancer. However, EGFR inhibitors were not effective in unselected patients with advanced NSCLC. After the identification of sensitizing EGFR mutations, tyrosine kinase inhibitors became the cornerstone of treatment for patients with EGFR-mutated NSCLC. However, other drugs were developed to target EGFR in the EGFR-wild type population, such as monoclonal antibodies. Cetuximab is an anti-EGFR monoclonal antibody, and has been a focus over the past two decades. Though not approved in NSCLC due to marginal and inconsistent effects in phase 3 trials, research aimed to discover biomarkers to identify a subgroup of the population that might benefit. This includes a composite score that evaluates histology, immunohistochemistry, and gene copy amplification. This article reviews the history of the development and discontinuation of monoclonal antibodies in NSCLC and discusses the role of biomarkers in the treatment of advanced EGFR-wild type NSCLC.