Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations
Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations
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DOI：
10.1200/jco.2012.44.2806
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发表时间：
2013-09-20
影响因子：
45.3
通讯作者：
Schuler, Martin
中科院分区：
文献类型：
--
作者：
Sequist, Lecia V.;Yang, James Chih-Hsin;Schuler, Martin
目的LUX-Lung 3研究比较了化疗与阿法替尼的疗效，阿法替尼是一种选择性、口服生物可利用的ErbB家族阻滞剂，可不可逆地阻断表皮生长因子受体（EGFR/ErbB 1）、人表皮生长因子受体2（HER 2/ErbB 2）和ErbB 4的信号传导，对EGFR突变具有广谱临床前活性。阿法替尼在EGFR突变阳性肺腺癌中的II期研究证明了高应答率和无进展生存期（PFS）。患者和方法在该III期研究中，筛选符合条件的IIIB/IV期肺腺癌患者的EGFR突变。突变阳性患者按突变类型（19号外显子缺失、L 858 R或其他）和人种（亚裔或非亚裔）分层，然后以2：1随机分配至40 mg阿法替尼/天或最多6个周期的顺铂+培美曲塞化疗（标准剂量，每21天一次）。主要终点是独立审查的PFS。次要终点包括肿瘤反应，总生存率，不良事件，和患者报告的结果（PROs）。结果共有1,269例患者进行了筛选，345例被随机分配到治疗。阿法替尼组的中位PFS为11.1个月，化疗组为6.9个月（风险比[HR]，0.58; 95% CI，0.43 - 0.78; P = .001）。19号外显子缺失和L 858 R EGFR突变患者（n = 308）的中位PFS，阿法替尼组为13.6个月，化疗组为6.9个月（HR，0.47; 95% CI，0.34 - 0.65; P = 0.001）。阿法替尼组最常见的治疗相关不良事件为腹泻、皮疹/痤疮和口腔炎，化疗组为恶心、疲乏和食欲下降。PRO赞成阿法替尼，更好地控制咳嗽，呼吸困难，和pain.ConclusionAfatinib与PFS的延长相比，标准的双联化疗在晚期肺腺癌和EGFR突变患者。(C)2013年美国临床肿瘤学会
PurposeThe LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).Patients and MethodsIn this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs).ResultsA total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatment-related adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain.ConclusionAfatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations. (C) 2013 by American Society of Clinical Oncology