Phase III Trial of Vandetanib Compared With Erlotinib in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer
Phase III Trial of Vandetanib Compared With Erlotinib in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2010.28.5981
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发表时间：
2011-03-01
影响因子：
45.3
通讯作者：
Goss, Glenwood D.
中科院分区：
文献类型：
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作者：
Natale, Ronald B.;Thongprasert, Sumitra;Goss, Glenwood D.
目的凡德他尼是一种每日一次的口服血管内皮生长因子受体和表皮生长因子受体信号传导抑制剂。这项 III 期研究评估了凡德他尼与厄洛替尼在未经选择的晚期非小细胞肺癌 (NSCLC) 患者中的疗效，这些患者先前接受过一到两种细胞毒性化疗方案治疗失败。 患者和方法 1240 名患者被随机分配接受凡德他尼 300 mg/d (n = 623) 或厄洛替尼 150 mg/d (n = 617)。主要目标是显示凡德他尼与厄洛替尼相比在无进展生存期 (PFS) 方面的优越性。如果差异未达到优越性的统计显着性，则进行非劣效性分析。 结果 与厄洛替尼相比，凡德他尼治疗患者的 PFS 没有显着改善（风险比 [HR]，0.98；95.22% CI，0.87 至 1.10；P = .721）；凡德他尼的中位 PFS 为 2.6 个月，厄洛替尼为 2.0 个月。次要终点总体生存率（HR，1.01；P = .830）、客观缓解率（均为 12%）以及疼痛症状恶化时间（HR，0.92；P = .289）、呼吸困难（HR，1.07；P = .407）和咳嗽（HR，0.94；P = .455）也没有显着差异。在预先计划的非劣效性分析中，两种药物均显示出相同的 PFS 和总生存率。凡德他尼比厄洛替尼更常见的不良事件（AE；任何级别）包括腹泻（分别为 50% vs 38%）和高血压（分别为 16% vs 2%）；厄洛替尼组皮疹发生率高于凡德他尼组（分别为 38% 和 28%）。凡德他尼的 3 级 AE 总体发生率也高于厄洛替尼（分别为 50% 和 40%）。 结论 在既往接受过治疗的晚期 NSCLC 患者中，凡德他尼显示出抗肿瘤活性，但与厄洛替尼相比并未表现出疗效优势。凡德他尼的一些 AE 发生率较高。 J 临床肿瘤杂志 29：1059-1066。 (c) 2011 年美国临床肿瘤学会
PurposeVandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This phase III study assessed the efficacy of vandetanib versus erlotinib in unselected patients with advanced non-small-cell lung cancer (NSCLC) after treatment failure with one to two prior cytotoxic chemotherapy regimens.Patients and MethodsOne thousand two hundred forty patients were randomly assigned to receive vandetanib 300 mg/d (n = 623) or erlotinib 150 mg/d (n = 617). The primary objective was to show superiority in progression-free survival (PFS) for vandetanib versus erlotinib. If the difference did not reach statistical significance for superiority, a noninferiority analysis was conducted.ResultsThere was no significant improvement in PFS for patients treated with vandetanib versus erlotinib (hazard ratio [HR], 0.98; 95.22% CI, 0.87 to 1.10; P = .721); median PFS was 2.6 months for vandetanib and 2.0 months for erlotinib. There was also no significant difference for the secondary end points of overall survival (HR, 1.01; P = .830), objective response rate (both 12%), and time to deterioration of symptoms for pain (HR, 0.92; P = .289), dyspnea (HR, 1.07; P = .407), and cough (HR, 0.94; P = .455). Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis. Adverse events (AEs; any grade) more frequent with vandetanib than erlotinib included diarrhea (50% v 38%, respectively) and hypertension (16% v 2%, respectively); rash was more frequent with erlotinib than vandetanib (38% v 28%, respectively). The overall incidence of grade = 3 AEs was also higher with vandetanib than erlotinib (50% v 40%, respectively).ConclusionIn patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib. J Clin Oncol 29:1059-1066. (c) 2011 by American Society of Clinical Oncology