Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial
Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial
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DOI：
10.1016/s1470-2045(13)70310-3
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发表时间：
2013-09-01
期刊：
影响因子：
51.1
通讯作者：
Marsoni, Silvia
中科院分区：
文献类型：
--
作者：
Garassino, Marina Chiara;Martelli, Olga;Marsoni, Silvia
背景厄洛替尼已注册用于治疗所有晚期非小细胞肺癌（NSCLC）患者。然而，其治疗肿瘤为EGFR野生型的患者（包括大多数患者）的疗效仍然存在争议。我们评估了厄洛替尼的疗效与标准的二线化疗在这样的patients.Methods，我们做了这个随机对照试验在52家意大利医院。我们招募了转移性NSCLC患者，他们接受过含铂化疗，并通过直接测序评估为野生型EGFR。患者在中心随机（1：1）接受厄洛替尼150 mg/d口服或多西他赛75 mg/m2静脉注射，每21天一次或每28天一次，第1、8和15天35 mg/m2。按中心、分期、一线化疗类型和体能状态对随机化进行分层。给予治疗或评估结果的患者和研究者不对治疗分配设盲，分析结果的研究者则对治疗分配设盲。主要终点是意向治疗人群的总生存期。该研究在ClinicalTrials.gov上注册，编号为NCT 00637910。结果我们筛选了702名患者，其中我们对540名患者进行了基因分型。222例患者入组（110例分配至多西他赛组，112例分配至厄洛替尼组）。多西他赛组的中位总生存期为8.2个月（95% CI 5.8-10.9），厄洛替尼组为5.4个月（4.5-6.8）（校正风险比[HR] 0.73，95% CI 0.53-1.00; p = 0.05）。多西他赛组的无进展生存期显著优于厄洛替尼组：多西他赛组的中位无进展生存期为2.9个月（95% CI 2.4-3.8），厄洛替尼组为2.4个月（2.1-2.6）（校正HR 0.71，95% CI 0.53-0.95; p = 0.02）。最常见的3-4级毒性反应为：中性粒细胞绝对计数低（多西他赛组21/104例[20%] vs厄洛替尼组107例无），皮肤毒性反应（无vs 15 [14%]），和乏力（10 [10%]对6 [6%]）。解释我们的结果表明，化疗比厄洛替尼更有效，既往接受过治疗的野生型EGFR肿瘤NSCLC患者的一线治疗。
Background Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of patients whose tumours are EGFR wild-type-which includes most patients-is still contentious. We assessed the efficacy of erlotinib compared with a standard second-line chemotherapy in such patients.Methods We did this randomised controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Patients were randomly assigned centrally (1:1) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2) every 21 days or 35 mg/m(2) on days 1, 8, and 15, every 28 days. Randomisation was stratified by centre, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation, investigators who analysed results were. The primary endpoint was overall survival in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT00637910.Findings We screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110 assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was 8.2 months (95% CI 5.8-10.9) with docetaxel versus 5.4 months (4.5-6.8) with erlotinib (adjusted hazard ratio [HR] 0.73, 95% CI 0.53-1.00; p = 0.05). Progression-free survival was significantly better with docetaxel than with erlotinib: median progression-free survival was 2.9 months (95% CI 2.4-3.8) with docetaxel versus 2.4 months (2.1-2.6) with erlotinib (adjusted HR 0.71, 95% CI 0.53-0.95; p = 0.02). The most common grade 3-4 toxic effects were: low absolute neutrophil count (21 [20%] of 104 in the docetaxel group vs none of 107 in the erlotinib group), skin toxic effects (none vs 15 [14%]), and asthenia (ten [10%] vs six [6%]).Interpretation Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours.