Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
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DOI：
10.1016/s1470-2045(11)70184-x
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发表时间：
2011-08-01
期刊：
影响因子：
51.1
通讯作者：
You, Changxuan
中科院分区：
文献类型：
--
作者：
Zhou, Caicun;Wu, Yi-Long;You, Changxuan
EGFR激活突变是非小细胞肺癌（NSCLC）患者对酪氨酸激酶抑制剂（TKI）治疗反应的重要标志。OPTIMAL研究比较了TKI厄洛替尼与标准化疗在晚期EGFR突变阳性NSCLC患者一线治疗中的疗效和耐受性。年龄大于18岁、经组织学证实的IIIB或IV期NSCLC和经证实的EGFR激活突变（19号外显子缺失或21号外显子L 858 R点突变）患者接受口服厄洛替尼（150 mg/天）治疗，直至疾病进展或出现不可接受的毒性反应，或接受最多4个周期的吉西他滨联合卡铂治疗。患者采用最小化程序随机分配（1：1），并根据EGFR突变类型、组织学亚型（腺癌vs非腺癌）和吸烟状态分层。主要结局是无进展生存期，在接受至少一剂研究治疗的确诊疾病患者中进行分析。该试验已在ClinicalTrials.gov注册，注册号为NCT 00874419，已完成入组;患者仍在随访中。结果83名患者随机分配接受厄洛替尼治疗，82名患者随机分配接受吉西他滨加卡铂治疗;厄洛替尼组82名患者和化疗组72名患者被纳入主要终点分析。厄洛替尼治疗患者的中位无进展生存期显著长于化疗患者（13.1 [95%CI 10.58-16.53] vs 4.6 [4.21-5.42]个月;风险比0.16，95%CI 0.10-0.26; p
Background Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.Methods We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT00874419, and has completed enrolment; patients are still in follow-up.Findings 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI 0.10-0.26; p