Gefitinib in non-small-cell lung cancer-an old lesson new re-visited.

Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer, and it is the most common cause of death in men and second only to breast cancer in women. Combination chemotherapy, usually platinum-based, is currently the first-line therapy of choice, however, the prognosis for patients with advanced NSCLC remains poor with a median survival time of 8-11 months and a 1-year survival rate of 30%. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC and has been the subject of considerable recent debate. The outstanding results of the JMEN study proved that maintenance of pemetrexed significantly improved the overall survival (OS) in advanced NSCLC patients was a proof of principle. Subsequently, the results of the SATURN study also showed a significant prolongation of progression-free survival (PFS) and OS with maintenance erlotinib compared with placebo. Despite considerable controversy, it has become an acceptable treatment paradigm and both drugs are approved for maintenance therapy of advanced NSCLC patients in Europe and the USA. In addition, several large phase III clinical trials (e.g., INFORM trial) provided evidence that maintenance therapy with gefitinib also significantly improved PFS in NSCLC patients, with greatest PFS benefit in patients harboring EGF-R mutations. However, OS was unchanged. The question still remains whether the benefit of maintenance therapy for NSCLC is best defined by PFS. Truely, PFS is the best predictor for improved OS (and is independent of subsequent treatment), but OS is acknowledged as the key clinical outcome in the treatment of advanced NSCLC. The approval of pemetrexed and erlotinib by the FDA and the EMEA and the promising data with gefitinib have certainly shifted the pendulum towards maintenance therapy, however, the precise role for the treatment strategy of NSCLC in terms of a maintenance approach is far from being clear and additional studies are warranted to further clarify this option.