What are the options for non-small-cell lung cancer patients post second-line therapy?

Abstract

10.2217/fon.15.159 © 2015 Future Medicine Ltd Lung cancer is a neoplasm characterized by uncontrolled growth, intrinsic antiblastic resistance and a high frequency of heterogeneity. These characteristics have led to a huge effort by clinicians for many years to perform clinical trials with experimental drugs, unfortunately without any real impact on survival outcomes. More recently many steps have been taken toward developing a deeper understanding of biological and genetic aspects of lung cancer, especially in non-small-cell lung cancers (NSCLCs). Nowadays, thanks to these discoveries, clinicians employ the term ‘precision medicine’ to define a biological drug with a great impact against diseases characterized by a genetic driver mutation. In the last few years, the knowledge about the targeted agents, such as the EGF receptor (EGFR) and ALK inhibitors, have led to the most impressive results increasing median overall survival beyond 24 months [1,2]. On the other hand, in the ‘nononcogene addicted’ population the maintenance strategy with pemetrexed allows a median overall survival of almost 18 months [3]. The molecular knowledge of lung cancer, along with properly employed targeted agents in oncogene addicted tumors and the maintenance strategy are the cornerstones that offer our patients more possibilities to live longer, with a better quality of life, as a result increasing the hope to receive several therapeutic lines after the first treatment attempt. Unfortunately, these improvements are more theoretical than applicable to daily clinical practice. In fact, despite a higher number of patients suitable for third-line therapies, the quantity and quality of a vailable drugs in this setting is poor. Actually, in many countries erlotinib is the only drug approved as third-line therapy. However, the population studied in the pivotal BR21 study [4] is probably not representative of a real practice patients population. It should be kept in mind that erlotinib was compared with best supportive care in a population not eligible for chemotherapy. Unfortunately, many trials published after the BR21 study did not manage to understand the real impact of a third-line therapy on clinical outcomes. In particular, the recently published DELTA trial tried to understand the role of docetaxel compared with erlotinib in an EGFR unselected pretreated population in second and third line. However, the study was not powered to observe a statistical COMMENTARY