Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial
Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial
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DOI：
10.1016/s1470-2045(09)70364-x
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发表时间：
2010-02-01
期刊：
影响因子：
51.1
通讯作者：
Fukuoka, Masahiro
中科院分区：
文献类型：
--
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
表皮生长因子受体（EGFR）基因突变的非小细胞肺癌患者对EGFR特异性酪氨酸激酶抑制剂吉非替尼反应良好。然而，吉非替尼是否优于标准铂双药化疗选择EGFR mutation.Methods的患者，我们做了一个开放标签，3期研究（WJTOG 3405）与2006年3月31日，2009年6月22日之间的招聘，在日本的36个中心。177例年龄≤ 75岁、诊断为IIIB/IV期非小细胞肺癌或术后复发携带EGFR突变的化疗初治患者（外显子19缺失或L 858 R点突变）随机分配，使用最小化技术，接受吉非替尼，（250 mg/天口服; n=88）或顺铂（80 mg/m2，静脉注射）加多西他赛（60 mg/m2，静脉注射; n=89），每21天给药一次，共3 - 6个周期。主要终点为无进展生存期。对改良的意向治疗人群进行生存分析。该研究在UMIN（日本大学医院医学信息网络）注册，编号000000539。结果5例患者被排除（2例患者随机分组后发现患有甲状腺癌和结肠癌，1例患者有外显子18突变，1例患者知情同意不充分，1例患者对多西他赛有急性过敏反应）。因此，172例患者（每组86例）被纳入生存分析。吉非替尼组的无进展生存期显著长于顺铂+多西他赛组，中位无进展生存期为9.2个月（95% CI 8.0-13.9）与6.3个月（5.8-7.8; HR 0.489，95% CI 0.336-0.710，对数秩p
Background Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor (EGFR) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib. However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain.Methods We did an open label, phase 3 study (WJTOG3405) with recruitment between March 31, 2006, and June 22, 2009, at 36 centres in Japan. 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned, using a minimisation technique, to receive either gefitinib (250 mg/day orally; n=88) or cisplatin (80 mg/m(2), intravenously) plus docetaxel (60 mg/m(2), intravenously; n=89), administered every 21 days for three to six cycles. The primary endpoint was progression-free survival. Survival analysis was done with the modified intention-to-treat population. This study is registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.Findings Five patients were excluded (two patients were found to have thyroid and colon cancer after randomisation, one patient had an exon 18 mutation, one patient had insufficient consent, and one patient showed acute allergic reaction to docetaxel). Thus, 172 patients (86 in each group) were included in the survival analyses. The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival time of 9.2 months (95% CI 8.0-13.9) versus 6.3 months (5.8-7.8; HR 0.489, 95% CI 0.336-0.710, log-rank p