Second-Line Treatment Options in Advanced Non-Small Cell Lung Cancer: Current Status

Despite the emergence of several antineoplastic drugs with activity in advanced non-small cell lung cancer (NSCLC), real progress with first-line therapy has been limited in the last decade. It has proven difficult to demonstrate important differences between third generation two-drug combinations. In contrast, progress with second-line therapy has been significant, especially in the past few years, with pemetrexed showing equivalent activity to docetaxel but with substantially less toxicity. At the same time, much work has been undertaken investigating the efficacy of the small-molecule epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib in the second-line and subsequent-line settings. Erlotinib has been shown to significantly improve survival versus placebo following failure on one or two prior regimens, especially in select or targeted patient populations. Finding the optimal place and patients for these agents in NSCLC treatment will be one of the more fascinating challenges of the next few years.