厄洛替尼辅助治疗与安慰剂对照用于 IB 期-IIIA 期非小细胞肺癌患者（RADIANT）：一项随机、双盲、III 期临床试验。
Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial.
机构信息
Karen Kelly, University of California, Davis, Comprehensive Cancer Center, Sacramento, CA; Nasser K. Altorki, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY; Wilfried E.E. Eberhardt, University Hospital Essen, Essen, Germany; Mary E.R. O'Brien, Royal Marsden Hospital, London, United Kingdom; David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Lucio Crinò, Ospedale S. Maria della Misericordia, Perugia, Italy; Chun-Ming Tsai, Taipei General Hospital and National Yang-Ming University, Taipei, Taiwan; Joo-Hang Kim, Yonsei University Health System, Seoul; Eun Kyung Cho, Gachon University, Incheon, Korea; Philip C. Hoffman, The University of Chicago Medical Center, Chicago; Jiuzhou Wang and Margaret A. Foley, Astellas Pharma, Northbrook, IL; Sergey V. Orlov, I.P. Pavlov Medical University, St Petersburg, Russia; Piotr Serwatowski, Specjalistyczny Szpital, Sokolowskiego, Szczecin, Poland; Julie D. Horan, Novella Clinical, Boulder, CO; and Frances A. Shepherd, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
出版信息
J Clin Oncol. 2015 Dec 1;33(34):4007-14. doi: 10.1200/JCO.2015.61.8918. Epub 2015 Aug 31.
PURPOSE
Epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitors have proven efficacy in advanced non-small-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting.
PATIENTS AND METHODS
An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive).
RESULTS
A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%).
CONCLUSION
Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRm-positive subgroup.
目的
表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂已被证明在晚期非小细胞肺癌（NSCLC）中具有疗效。我们假设厄洛替尼在辅助治疗中会有效。
患者和方法
这项国际、随机、双盲、安慰剂对照研究纳入了完全切除的 IB 至 IIIA 期 NSCLC 患者，这些患者的肿瘤通过免疫组织化学法检测到 EGFR 蛋白表达或通过荧光原位杂交法检测到 EGFR 扩增。患者按 2:1 的比例随机分配至厄洛替尼 150 mg 每日 1 次或安慰剂组，治疗时间为 2 年。分层因素包括分期、组织学、既往辅助化疗、吸烟状态、EGFR 扩增状态和国家。主要终点为无病生存期（DFS）；关键次要终点为总生存期（OS）和有 EGFR 激活突变（EGFRm 阳性）患者的 DFS 和 OS。
结果
共纳入 973 例患者（2007 年 11 月 26 日至 2010 年 7 月 7 日）。厄洛替尼组和安慰剂组的 DFS 无统计学显著差异（中位值分别为 50.5 个月和 48.2 个月；风险比为 0.90；95%CI 为 0.74 至 1.10；P=0.324）。在 EGFRm 阳性亚组的 161 例患者（16.5%）中，厄洛替尼组的 DFS 更优（中位值分别为 46.4 个月和 28.5 个月；风险比为 0.61；95%CI 为 0.38 至 0.98；P=0.039），但由于分层检验程序，该差异无统计学意义。OS 数据尚不成熟。厄洛替尼组的皮疹和腹泻发生率分别为 528 例（86.4%）和 319 例（52.2%），而安慰剂组的发生率分别为 110 例（32.1%）和 54 例（15.7%）。厄洛替尼组最常见的 3 级不良事件是皮疹（22.3%）和腹泻（6.2%）。
结论
厄洛替尼辅助治疗未能延长 EGFR 表达的 NSCLC 患者或 EGFRm 阳性亚组患者的 DFS。有必要在 EGFRm 阳性亚组中进一步评估厄洛替尼。
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