A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer
A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2013.08.002
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发表时间：
2013-11-01
期刊：
影响因子：
5.3
通讯作者：
Thatcher, N.
中科院分区：
文献类型：
--
作者：
Ciuleanu, T.;Tsai, C. -M.;Thatcher, N.
背景：分子靶向药物治疗非小细胞肺癌（NSCLC）可以提供与化疗相似的疗效，而没有化疗相关的毒性。联合两种不同作用方式的药物可以进一步提高这些治疗的疗效。TASK研究评估了表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼联合抗血管生成药物贝伐单抗作为未选择的晚期非鳞状NSCLC患者一线治疗的疗效和安全性。方法：于2007年12月至2008年9月招募患者。计划样本量为200例患者，共124例患者被随机化。患者采用1:1的最小化算法随机接受贝伐单抗（每21天周期第1天静脉注射15mg /kg）加化疗（吉西他滨/顺铂或卡铂/紫杉醇标准剂量，4-6个周期）（BC组）或贝伐单抗加厄洛替尼（口服150mg /天；BE组），直到疾病进展或不可接受的毒性。主要终点为无进展生存期（PFS）。如果在预先计划的中期分析中，BE相对于BC的PFS风险比（HR）高于1.25，有利于BC，则应重新评估该研究。次要终点包括总生存期、有效率和安全性。结果：所有随机患者（n = 63 BE; n = 61 BC）进行疗效评估分析。在更新的中期分析中，BE和BC的中位PFS分别为18.4周（95%可信区间[CI] 17.0-25.1）和25.0周（95% CI 20.6-[未达到]）（死亡或疾病进展的HR， BE相对于BC， 2.05, p = 0.0183）。BE治疗的死亡率为19%，而BC治疗的死亡率为11.5%。在更新的中期分析中，PFS的HR高于1.25，因此BE组的患者被允许改变组或切换到另一种药物，研究终止。不良事件的报告与预期一致。结论：TASK研究未显示厄洛替尼联合贝伐珠单抗在未选择的一线晚期非鳞状NSCLC的PFS方面比化疗加贝伐珠单抗有益处。(C) 2013年作者。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients.Methods: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15 mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150 mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety.Results: All randomized patients (n = 63 BE; n = 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p = 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected.Conclusions: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab. (C) 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.