The search for improved systemic therapy of non-small cell lung cancer--what are today's options?

Although stage IV non small cell lung cancer (NSCLC) remains an incurable disease and drug resistance ultimately develops, important steps forward have been made within the last few years. The number of new active agents is rapidly increasing and the area of personalized medicine has definitively arrived. Treatment choices are starting to be made upon tumour characteristics, and more effective and better tolerated agents are now available. In the molecular era we are facing many new challenges: The availability of sufficient tissue, which is often not easily accessible in a tumour arising from an internal organ, sensitivity and specificity of biomarker testing, heterogeneity of marker profiles between primary tumour and metastases or even within a single tumour mass, application and reproducibility of the correct biomarker test method and the differentiation of the predictive vs. the prognostic value of biomarkers. Unfortunately, the development of new targeted agents frequently continues to be performed in unselected patient populations, lacking the early identification of relevant predictive molecular biomarkers. Consequently, thousands of patients are enrolled into clinical trials with a low probability of success. This overview will focus on the most recent new systemic treatment options in NSCLC, including the role of pemetrexed, bevacizumab, cetuximab, maintenance therapy and tyrosine kinase inhibitors in patients with an activating epidermal growth factor receptor mutation. In addition, emerging treatment strategies will be described.