Integration of EGFR Inhibitors and Conventional Chemotherapy in the Treatment of Non-Small-cell Lung Cancer

Introduction/Background: Given the limited gains of traditional chemotherapy in improving outcomes in patients with advanced non-small-cell lung cancer (NSCLC), recent research efforts have investigated the integration of targeted agents into the treatment algorithm. Materials and Methods: Searches of PubMed and of recent results from key oncology congresses were performed to identify relevant articles and abstracts. Initial phase III trials combining the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib with platinum-based doublets as first-line therapy failed to demonstrate an overall survival advantage in unselected patients with NSCLC. However, in recent years, there has been substantial progress in understanding the determinants of response to EGFR TKI therapy, including the presence of activating EGFR mutations, which has been reflected in clinical trials specifically evaluating these patient populations. In addition, evidence suggesting potential mechanistic interference between concurrent EGFR TKIs and chemotherapy has also been observed, fueling interest in sequential or intermittent dosing. EGFR-targeted agents such as the multitargeted TKI vandetanib and the next-generation EGFR TKIs afatinib (BIBW 2992) and PF00299804 are also under clinical investigation for the treatment of NSCLC, both alone and in combination with chemotherapy. Conclusions: Trials evaluating various regimens of EGFR-targeted agents and chemotherapy are planned and/or underway and will hopefully define the role of integrated therapy in NSCLC.