Role of erlotinib in the treatment of advanced non-small-cell lung cancer patients with EGFR wild-type tumors

EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment paradigm of non-small-cell lung cancer (NSCLC). The observation of a rapid response to single-agent EGFR TKIs led to the discovery of EGFR-activating mutations, with subsequent studies showing superior progression-free survival in treatment-naive patients with EGFR mutation-positive NSCLC treated with EGFR TKIs versus platinum doublets. On the basis of these findings it has been suggested that the benefit associated with EGFR TKI therapy in unselected NSCLC patients is limited to the subset of patients with EGFR mutation-positive disease. However, studies with erlotinib, a reversible EGFR TKI, have shown that while the drug is associated with a relatively low response rate in patients with EGFR wild-type tumors there is evidence to suggest that it has a positive impact on survival. Evidence supporting the clinical benefit of erlotinib in patients with EGFR wild-type tumors is discussed in this review.