Recent clinical developments and rationale for combining targeted agents in non-small cell lung cancer (NSCLC)

While chemotherapy has been the standard of care for patients with advanced non-small cell lung cancer (NSCLC), efforts have shifted toward evaluating novel targeted agents in an attempt to improve outcome. These targeted agents are directed toward key components in several signalling pathways such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-IR). There is also increasing interest in using combinations of targeted agents to inhibit more than one pathway; for example, inhibition of VEGFR + EGFR and VEGFR + PDGFR + EGFR. Further investigation is needed to identify the most appropriate combinations of these targeted agents in select patient subgroups, and to define optimal treatment doses to thereby achieve the best therapeutic index. This review outlines the rationale for combining targeted agents for the treatment of advanced NSCLC.

► Novel targeted agents are being evaluated for advanced NSCLC to improve outcomes. ► These targeted agents are directed toward key components in signalling pathways, such as VEGFR, PDGFR, EGFR, and IGF-IR. ► Primary or acquired resistance to individual targeted agents results in loss of efficacy. ► Early evidence shows promise for combinations of targeted agents that inhibit more than one signalling pathway. ► Predictive markers of response are being identified, so future therapies can be tailored to each individual patient.