Systemic therapies in metastatic non-small-cell lung cancer with emphasis on targeted therapies: the rational approach

Historically, first-line treatment of non-small-cell lung cancer (NSCLC) has been based on giving a limited number of cycles of chemotherapy to achieve tumour response or stable disease. Patients are then observed without active therapy until disease progresses, at which point, subsequent lines of therapy are given. In recent years, two new concepts have been introduced to the management of NSCLC: maintenance therapy and therapy with targeted agents. Maintenance therapy-with either a chemotherapeutic or biologic agent-is given immediately after first-line therapy to patients who have achieved tumour response or stable disease. Choice of therapy may include continuation of the agents included in the induction regimen or introduction of different agents (early second-line treatment) with the aim of preventing progression and prolonging progression-free survival. Targeted agents such as bevacizumab and erlotinib target critical molecular signalling pathways and provide several advantages over chemotherapy, including fewer toxicities and the possibility of a longer duration of therapy. This review examines the treatment options in all lines of therapy for metastatic NSCLC, focusing particularly on targeted therapies that have been approved in the United States, Canada, or Europe.