Role of afatinib in the treatment of advanced lung squamous cell carcinoma

Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and anti-angiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors. Considering the role of the ErbB-signaling cascade in lung SqCC, it is relevant to note that ErbB1 (epidermal growth factor receptor [EGFR]) is overexpressed in 85% of non-small-cell lung carcinomas (NSCLCs), particularly in patients with squamous histology, and is associated with poor prognosis. For this reason, EGFR activity has been investigated as a therapeutic strategy in lung SqCC. Even taking into account statistically positive trial results, anti-EGFR approach still remains controversial in unselected/wild-type EGFR lung SqCC patients, as well as the optimal timing and sequencing of all available targeted therapies considering the approval of immunotherapeutic agents. This review analyzes current data about EGFR inhibition in lung SqCC with a specific focus on afatinib in order to elucidate available clinical evidence supporting EGFR targeting in this setting as well as a future management of advanced lung SqCCs in the context of new emerging immunotherapeutic drugs.