Optimizing Therapy in Previously Treated Non-Small Cell Lung Cancer

The past decade has seen the identification of several novel cytotoxic agents. More recently, targeted therapies with single-agent activity or that enhance the efficacy of chemotherapy in advanced non-small cell lung cancer have been identified. These agents have been, or are undergoing, active testing alone and in combination in both loco-regional and advanced disease as initial therapy and after failure of cytotoxic therapy. The cytotoxic agents docetaxel, pemetrexed, and topotecan, as well as the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, have been evaluated in phase III trials in previously treated populations. This review summarizes the results of these phase III studies with a particular focus on predictors of favorable outcome, attempts to provide a rational approach to therapeutic selection in this patient population, and discusses ongoing pivotal trials and future strategies in this field.