A number of important changes in first-line treatment of advanced non-small cell lung cancer (NSCLC) have occurred. Pemetrexed with cisplatin has become the standard for first-line treatment in nonsquamous cell carcinoma, and gefitinib has become the treatment of choice for patients with sensitizing epidermal growth factor receptor (EGFR) mutations. The choice of pemetrexed is based on overall survival (OS) and improvement in toxicity, while the choice for gefitinib is based on increased progression-free survival (but not OS), together with quality-of-life benefits, in NSCLC patients with sensitizing mutations. In a subgroup analysis of the Eastern Cooperative Oncology Group (ECOG) 4599 trial with carboplatin/paclitaxel, bevacizumab has been associated with a median survival of 14.2 versus 10.3 months with chemotherapy (CT) alone. However, the AVAstin in Lung cancer (AVAiL) trial with gemcitabine/cisplatin did not have an OS benefit. Nevertheless, safety and clinical activity with a median survival of 14.2 months has been confirmed in the Safety of Avastin in Lung cancer (SAIL) trial with a variety of CT regimens.
Another great change has been the effect of maintenance therapy following initial CT. Pemetrexed maintenance was associated with increased survival of 5.2 months over placebo in nonsquamous cell tumors when pemetrexed was not used in the initial treatment. In the erlotinib maintenance trial there was also an improvement in OS, particularly marked in the stable disease group that was independent of EGFR mutation status.
There has been no real advance in the treatment of poor performance status (PS) patients, although elderly patients with a good PS can benefit from doublet platinum-based CT. In terms of future outlook, a number of trials are assessing the effect of the new agents. However, a challenge for the future is for the relevant biomarkers to be assessed in routine pathology laboratories. Issues of tissue collection, biopsy size, standardization, and accessibility of the techniques remain to be formalized. Furthermore, the hierarchy of testing on a sequential approach is likely to be too lengthy for aggressive NSCLC. The testing of multiple biomarkers in a single phase will be required in the future. Nevertheless, NSCLC treatment is now at a stage of rapid development and more patients than ever are benefiting from the new treatment approaches.