First-line Systemic Therapy for Metastatic Non-small-cell Lung Cancer - A Review

Our aim was to review and update the current status of systemic therapy for metastatic non-small-cell lung cancer (NSCLC). We reviewed Phase II or Phase III clinical trials of first-line third-generation chemotherapy regimens (docetaxel, gemcitabine, paclitaxel, pemetrexed, and vinorelbine) and targeted agents (bevacizumab, cetuximab, erlotinib, and gefitinib) identified through Medline, international conferences, and websites of related organizations. We found effort should be taken to find out whether patients have a tumor epidermal growth factor receptor (EGFR)-active mutation. EGFR-tyrosine kinase inhibitor could be given as first-line treatment for patients with active EGFR mutations (Exon 19 deletions and Exon 21 L858R), whereas patients with a good performance status and wild-type or unknown EGFR mutation status should be treated with platinum-based doublets (platinum plus a third-generation chemotherapy agent). No specific third-generation agent is clearly superior for use in combination with a platinum agent. However, pemetrexed is more active in nonsquamous NSCLC. The survival advantage of platinum-based doublets over non-platinum combinations or older combinations is modest. Systemic chemotherapy beyond four to six cycles impedes quality of life without prolonging life. However, data suggest switching to maintenance with pemetrexed or erlotinib therapy is effective in prolonging patient survival. The addition of bevacizumab to carboplatin and paclitaxel has shown improved survival, and a large-scale Phase IV study showed the efficacy and safety of the combination of bevacizumab with platinum-based doublets. In conclusion, in tumor EGFR-mutated NSCLC, EGFR-tyrosine kinase inhibitor is the first-line treatment of choice for patients with metastatic disease. The combination of a platinum agent plus a third-generation agent continues to be the standard of care for those patients with tumor EGFR wild-type or unknown status. Pemetrexed is more active in patients with non-squamous NSCLC, and bevacizumab in combination with platinum-based doublets can also be considered in patients with non-squamous NSCLC. As differences between the regimens are small, a detailed discussion with the patient regarding treatment toxicity and patient preference will help in making the regimen choice.