Salvage therapy for advanced non-small cell lung cancer: factors influencing treatment selection

Novel chemotherapies and molecularly targeted agents have improved outcomes for patients with advanced non-small cell lung cancer (NSCLC). Several efficacious regimens are available, which allows for selection of therapy based on factors such as schedule, toxicity profile, patient-specific needs, and individual preferences of the patient. Treatment guidelines recommend platinum-based chemotherapy first line for patients with a good performance status. These regimens offer a modest survival advantage over best supportive care. The role of targeted biologic agents in this setting is being assessed in phase II trials. Results to date show promising activity and tolerability. Erlotinib, docetaxel, and pemetrexed are all approved for patients who progress following one prior regimen for advanced NSCLC. These agents have different tolerability profiles and routes of administration but appear to have similar effects on tumor response and survival, though comparative trials are required to confirm this. Based on the results of a phase III trial, erlotinib is also recommended for third-line use in patients with NSCLC. Identifying predictive markers of clinical response to therapy may provide an opportunity to better select patient subsets appropriate for specific treatment. Recent data have linked various clinical characteristics and biologic markers with outcome to HER-1/EGFR-targeted agents. However, many of these studies are retrospective and based on small patient numbers, and there is evidence of broad benefit across diverse patient subgroups with erlotinib. Prospective, randomized trials are required to validate potential predictive markers fully before they are applied to clinical practice.