Ishibe Naoko, Carlson Josh, Ramsey Scott David, Freedman Andrew, Schully Sheri
Program Director, CTEB, DCCPS, National Cancer Institute, NIH, Bethesda, MD; Institute of Public Health Genetics, School of Public Health and Community Medicine, University of Washington, Seattle, WA; Physician, Health Services Researcher; Genomic Pharmacoepidemiology, US National Cancer Institute and Health Sciences Administrator, NCI, Bethesda, MD.
PLoS Curr. 2011 Jun 21;3:RRN1245. doi: 10.1371/currents.RRN1245.
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in the United States. Moreover, advanced non-small-cell lung cancer (NSCLC) is considered an incurable disease and current treatment approaches provide marginal improvement in overall survival at the expense of substantial morbidity and mortality, highlighting the need for new, less toxic treatment approaches. Tyrosine kinase inhibitors, such as erlotinib (Tarceva®), have been developed and approved as maintenance, second- and third-line treatment options in unselected advanced NSCLC patients (2, 15). However, subgroup analyses from the initial clinical trials consistently showed that patients with epidermal growth factor receptor (EGFR) mutations who received erlotinib had higher rates of response and better progression-free and overall survival, leading to clinical trials specifically focused on the use of tyrosine kinase inhibitors as first-line therapy in these patients. We examined the published literature on the analytic validity, clinical validity, and clinical utility of EGFR mutational testing in guiding first-line therapy use of erlotinib to treat advanced NSCLC and we briefly summarized the current lung cancer screening guidelines. The primary goal was to provide a basic overview of EGFR mutational testing and use of erlotinib as first-line therapy and identify gaps in knowledge and evidence that affect the recommendation and adoption of the test in advanced NSCLC treatment management strategies.
肺癌是美国第二常见的癌症，也是癌症相关死亡的主要原因。此外，晚期非小细胞肺癌（NSCLC）被认为是一种无法治愈的疾病，目前的治疗方法虽能在一定程度上提高总生存率，但会带来较高的发病率和死亡率，这凸显了需要新的、毒性较小的治疗方法。酪氨酸激酶抑制剂，如厄洛替尼（特罗凯®），已被开发并批准作为未选择的晚期NSCLC患者的维持治疗、二线和三线治疗选择（2, 15）。然而，最初临床试验的亚组分析一致显示，接受厄洛替尼治疗的表皮生长因子受体（EGFR）突变患者有更高的缓解率以及更好的无进展生存期和总生存期，这促使开展了专门针对酪氨酸激酶抑制剂作为这些患者一线治疗的临床试验。我们研究了已发表的关于EGFR突变检测在指导厄洛替尼一线治疗晚期NSCLC中的分析有效性、临床有效性和临床实用性的文献，并简要总结了当前的肺癌筛查指南。主要目的是提供EGFR突变检测及厄洛替尼作为一线治疗的基本概述，并找出影响该检测在晚期NSCLC治疗管理策略中的推荐和应用的知识与证据方面的差距。
