Achieving Response and Improving Outcomes of First-line Therapy for Advanced Non–small-cell Lung Cancer

Full Article

KK Loh

Hong Kong J Radiol 2013;16(Suppl):S23-8

The first-line treatment paradigm for advanced non–small-cell lung cancer (NSCLC) has evolved in the past few decades, with marked improvements in therapeutic strategies and choice of active agents. Prior to the 1990s, few cytotoxic agents were available with activity against NSCLC. The era of systemic chemotherapy for NSCLC evolved when doublet chemotherapy, combining a platinum agent and a ‘third-generation’ agent, became the standard of care for patients with advanced NSCLC. Studies involving pemetrexed, one of the newer cytotoxic agents effective in non-squamous NSCLC, show that treatment selection based on histology provides survival benefit. There has also been major progress in understanding the disease pathogenesis on the molecular level, which led to the discovery of ‘actionable’ mutations associated with response and a new vista for the development of targeted therapy. For mutation-negative advanced NSCLC, bevacizumab is the first agent to demonstrate significant survival benefit and improved response when used in combination with platinum-based doublet chemotherapy. Maintenance therapy with chemotherapy or a targeted agent following four to six cycles of firstline treatment is a recent approach that has gained extensive interest. Accumulating evidence indicates that bevacizumab is an effective option in both first-line and maintenance settings. This article reviews the recent advances in first-line treatment of advanced NSCLC that lacks actionable mutations, and discusses the emerging role of maintenance therapy to further improve lung cancer outcomes.