2014年ASCO大会中的肺癌口头报告中，有一项报告对LUX-Lung3和LUX-Lung6进行了汇总分析，给出了更多关于阿法替尼治疗常见EGFR突变晚期NSCLC患者OS的数据。下面和大家提前分享这项研究。

背景：

阿法替尼（A）是一种口服的、不可逆的针对EGFR、HER2、ErbB3和ErbB4信号通路的ErbB家族抑制剂。LUX-Lung3（LL3）研究比较了阿法替尼和顺铂/培美曲塞在全球345个病人中的疗效，LUX-Lung6（LL6）研究比较了阿法替尼和吉西他滨/顺铂在364名亚洲病人中的疗效。初步分析（2012）显示，所有EGFR突变人群中阿法替尼相比于化疗的PFS优势(HR=0.58[LL3],HR=0.28[LL6])，有常见EGFR突变（Del19/L858R）病人的PFS也升高（HR=0.47 [LL3], HR=0.25 [LL6]）。FDA已经批准阿法替尼用于EGFR突变晚期NSCLC患者的一线治疗。本研究中我们对这类病人的已成熟的OS数据进行了汇总分析。

方法：

未经治疗的EGFR突变的IIIB/IV期NSCLC病人以2:1随机分配到40mg阿法替尼，或者6个周期的标准化疗，通过EGFR突变和种族进行分层（LL3）。主要终点是PFS，而OS是一种关键的次要终点。记录不良反应。

结果：

该汇总分析包括了631名常见EGFR突变（Del19=355, L858R=276）病人随机进入LL3和LL6；419名病人接受阿法替尼，212名接受化疗。在开始分析时（2014年1月），404名（64%）病人死亡。OS中位随访期为36.5个月。随着进展，78%病人接受后续的系统治疗；化疗组的68%病人接受EGFR-TKI药物，阿法替尼组的70%病人接受化疗。阿法替尼组相比化疗组的OS明显延长（中位OS：27.3 vs 24.3个月，HR=0.81[CI 0.66,0.99]，p=0.037）。LL3和LL6的单独HR与汇总分析的一致。

在Del19的病人中，HR=0.59(CI 0.45, 0.77; p<0.001) ；L858R病人，HR=1.25 (CI 0.92, 1.71; p=0.160)。更新的PFS和安全性数据与之前的主要报告一致。

结论：

该汇总分析显示，一线阿法替尼可以显著提高有常见EGFR突变（Del19/L858R）晚期NSCLC患者的OS。这是首次分析显示对EGFR突变病人进行基因型导向治疗可以改善生存。临床试验信息：NCT00949650。

医脉通整理报道，转载请注明出处。

会议专题》》》2014年ASCO年会专题报道

阅读摘要原文

Overall survival (OS) in patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring common (Del19/L858R) epidermal growth factor receptor mutations (EGFR mut): Pooled analysis of two large open-label phase III studies (LUX-Lung 3 [LL3] and LUX-Lung 6 [LL6]) comparing afatinib with chemotherapy (CT).(Abstract No:8004^)

Author(s): James Chih-Hsin Yang, Lecia V. Sequist, Martin H. Schuler, et al.

Session Type: Oral Abstract Session

Background: Afatinib (A) is an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling. LL3 compared A with cisplatin/pemetrexed in 345 pts recruited globally and LL6 compared A with gemcitabine/cisplatin in 364 Asian pts. The primary analysis (2012) showed improved progression-free survival (PFS) with A versus CT in the overall EGFR mut positive population (HR=0.58 [LL3], HR=0.28 [LL6]) and pts with common (Del19/L858R) EGFR mut (HR=0.47 [LL3], HR=0.25 [LL6]). The FDA has approved A for the first-line treatment of pts with advanced NSCLC harboring common EGFR mut. Here we present a pooled analysis of mature OS data among such pts. 

Methods: Treatment-naïve pts with EGFR mut stage IIIB/IV NSCLC were randomized 2:1 to 40 mg A or up to 6 cycles of standard CT and stratified by EGFR mut and race (LL3). The primary endpoint was PFS, with OS as a key secondary endpoint. Adverse events were also recorded. 

Results: The pooled analysis included 631/709 pts randomized into LL3 and LL6 with common EGFR mut (Del19=355, L858R=276); 419 pts received A and 212 received CT. At the time of analysis (January 2014), 404 (64%) pts had died. Median follow-up for OS was 36.5 months. Following progression, 78% of pts received subsequent systemic therapies (median of 3 regimens); 68% in the CT group received EGFR TKIs and 70% in the A group received CT. OS was significantly improved with A versus CT (median 27.3 vs 24.3 months, HR=0.81 [CI 0.66, 0.99; p=0.037]). Individual HRs for OS in LL3 and LL6 were consistent with the pooled analysis. Among Del19 pts the HR=0.59 (CI 0.45, 0.77; p<0.001) and in L858R pts the HR=1.25 (CI 0.92, 1.71; p=0.160). Updated PFS and safety findings were consistent with earlier primary reports. 

Conclusions: This pooled analysis reveals that first-line A significantly improves OS in pts with advanced NSCLC harboring common EGFR mut (Del19/L858R) compared with CT. This is the first analysis to show that genotype-directed therapy for EGFR mut pts can improve survival. Clinical trial information: NCT00949650.

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