Integrating Epidermal Growth Factor Receptor–Targeted Therapies into Platinum-Based Chemotherapy Regimens for Newly Diagnosed Non–Small-Cell Lung Cancer

Cytotoxic chemotherapy treatment for patients with advanced non–small-cell lung cancer (NSCLC) has reached a plateau, but further improvements are expected with integration of targeted therapies. Epidermal growth factor receptor (EGFR)–directed therapies are of particular interest because the EGFR is frequently expressed in tumors and associated with poorer outcome. Thus, blockade of the EGFR should improve outcome. Blockade can be achieved by tyrosine kinase inhibitors (TKIs) or monoclonal antibodies (MoAbs). Both approaches have been evaluated in advanced NSCLC. As single agents, EGFR-directed TKIs have demonstrated efficacy in patients previously treated with chemotherapy. When combined with firstline platinum-based chemotherapy, TKIs failed to improve the outcome. In contrast, MoAbs in combination with platinum-based first-line chemotherapy showed promising efficacy in phase II trials. Two phase III trials with chemotherapy with or without cetuximab have been performed in patients with advanced NSCLC. Other EGFR-directed MoAbs and TKIs are in earlier stages of clinical development.