Achieving Response and Improving Outcomes of First-line Therapy for Advanced Non–small-cell Lung Cancer
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.
中文摘要
晚期非小細胞肺癌的一線治療達至有效及改善結果
陸凱祖
九十年代前只有數種針對晚期非小細胞肺癌（NSCLC）的細胞毒性藥物。在過去數十年NSCLC的一線治療模式漸漸進化，大大改善了治療策略和有效藥物的選擇。當雙藥化療結合鉑劑和「第三代」藥物成為治療晚期NSCLC的標準後，NSCLC的全身治療進入了新的年代。培美曲塞（pemetrexed）是一種較新的針對非鱗狀NSCLC的細胞毒性藥物，根據組織學以選擇治療的研究顯示，培美曲塞能提供更佳的生存優勢。從分子水平上對於發病機制的理解增加，導致發現「可操作」突變與治療反應相關，並有助針對性的治療發展。對於突變呈陰性的晚期NSCLC患者，與鉑類雙藥化療結合使用時，貝伐單抗（bevacizumab）是首個顯示出更佳生存優勢及治療反應的藥物。四至六個週期的一線治療後再施以化療或靶向藥物作維持治療，近期經已獲得廣泛關注。越來越多的證據顯示，貝伐珠單抗是在第一線和維持治療的一個有效選擇。本文回顧缺乏「可操作」突變的晚期NSCLC在第一線治療的最新研究進展，並討論維持治療在進一步提高肺癌預後的新功能。