Advanced NSCLC: A continuum from first-line to relapse treatment

The management of advanced non-small cell lung cancer (NSCLC) has progressed over the last 3 decades. Advances in chemotherapeutic drugs and the use of multi-drug combinations, biological agents and new management strategies have provided modest survival benefits. However, improving quality of life is equally important, and involves a therapeutic strategy that considers the optimal balance between treatment activity (survival, symptom control) and treatment burden (side effects, duration of hospital stay). There remains room for improvement of our current standard approach with platinum doublets, given that the 1-year survival is approximately 35 %.

In first-line treatment, the option of adding more cytotoxic agent to a platinum-based doublet does not appear to improve survival, but increases toxicity. With the advent of biological drugs, there is much interest in adding such an agent – targeting either the EGFRaxis or the angiogenesis pathway – to the current standard platinum doublets.

As for relapse therapy, just 10 years ago very few patients with advanced NSCLC were candidates for second-line treatment. However, as response rates and toxicity profiles with first-line therapies improved, relapse treatment has become more important. Several single agent chemotherapies have been evaluated in the second-line setting, including the antimetabolite pemetrexed, which demonstrates comparable survival outcomes to that of the historical standard docetaxel, but a much better toxicity profile. The targeted therapies gefitinib and erlotinib are other options in this setting. Further studies, especially focusing on clinical and biological predictive factors are required to establish the role of newer options in the management of advanced NSCLC, so that the most logical continuum of treatment can be offered to each patient.