(LUX-Lung 7)：阿法替尼一线治疗EGFR突变非小细胞肺癌患者，显著优于吉非替尼【翻译】
(LUX-Lung 7)：阿法替尼一线治疗EGFR突变非小细胞肺癌患者，显著优于吉非替尼翻译：韩晓晨（lunaeleven）
一项于2016年4月12日在线发表于《柳叶刀（The Lancet）》期刊的头对头研究报告，阿法替尼（BIBW2992）一线治疗EGFR突变非小细胞肺癌患者，效果显著优于吉非替尼。
本研究旨在比较吉非替尼和阿法替尼用于EGFR驱动的非小细胞肺癌一线治疗的效果与安全性。这项2B期国际多中心随机双盲试验（试验编号：NCT01466660）在2011年11月13日至2013年8月8日间，招募了来自13个国家、64个中心的319位3B期和4期非小细胞肺癌患者。这些患者均未经治疗，且伴有常见EGFR突变（19外显子缺失或21-L858R外显子突变）。
被试患者按照1:1的比例随机分为两个治疗组，一组接受每日40mg的阿法替尼治疗，另一组接受每日250mg的吉非替尼治疗，直至病情进展或出现不可耐受的不良反应。
本试验中位随访时间为27.3个月（15.3–33.9）。无进展生存期（PFS）方面，阿法替尼组为11个月（95% CI 10.6–12.9），吉非替尼（9.1–11.5）组为10.9个月。治疗起始至失败的时间，阿法替尼组为13.7个月 （95% CI 11.9–15.0），显著长于吉非替尼组11.5个月 （10.1–13.1）。截至发表时间，最终生存数据尚未成熟。
最常见的与治疗相关的三级或四级副作用包括腹泻（阿法替尼组160名患者中发生率为13%，N=20;吉非替尼组159名患者中发生率为1%，N=2）；皮疹或痤疮样疹（阿法替尼组发生率为9%，N=15；吉非替尼组为3%，N=5）和肝酶升高（阿法替尼组发生率为0，吉非替尼组为9%，N=14）。
与治疗有关的严重副作用在阿法替尼组为11%（N=17），吉非替尼组为4%（N=7）。每组中各有6%的患者因与药物有关的副作用终止治疗。
致命性副作用方面。阿法替尼组的发生率为9%（N=15），而吉非替尼组为6%（N=10）。所有致命性副作用中，仅一例被认为与治疗相关。该患者死于吉非替尼治疗引发的药物性肝肾衰竭。
相比吉非替尼，阿法替尼一线治疗显著提升了EGFR突变的非小细胞肺癌患者的治疗效果，且副作用可控。此结论对于EGFR突变患者的临床治疗具有潜在的重要指导意义。
原文链接：http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30033-X/abstract
原文摘要：
Summary
Background
The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting.
Methods
This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660.
Findings
Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months with afatinib vs 10·9 months with gefitinib; hazard ratio 0·73 , p=0·017) and time-to-treatment failure (median 13·7 months with afatinib vs 11·5 months with gefitinib; HR 0·73 , p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 of 160 patients given afatinib vs two of 159 given gefitinib) and rash or acne (15 patients given afatinib vs five of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure.
Interpretation
Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.
Funding
Boehringer Ingelheim. 晨，牛掰。妈妈目前2992中，学习了。 那以后是不是一线要用易瑞沙额就直接用2992替代服用啊？
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