Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial
Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial
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DOI：
10.1200/jco.2010.29.5717
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发表时间：
2011-03-01
影响因子：
45.3
通讯作者：
Vansteenkiste, Johan F.
中科院分区：
文献类型：
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作者：
de Boer, Richard H.;Arrieta, Oscar;Vansteenkiste, Johan F.
目的凡德他尼是一种每日一次口服的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。这项随机、安慰剂对照的III期研究评估了凡德他尼加培美曲塞作为晚期非小细胞肺癌二线治疗的疗效。Patients and MethodsPatients（N = 534）被随机分配接受凡德他尼100 mg/d加培美曲塞500 mg/m2每21天一次（n = 256）或安慰剂加培美曲塞（n = 278）。无进展生存期（PFS）是主要终点;总生存期，客观反应率，疾病控制率，症状恶化的时间，和secondary assessment.ResultsThere是PFS治疗组之间没有显着差异（风险比[HR]，0.86; 97.58%CI，0.69至1.06; P = 0.108）。总生存期也没有显著差异（HR，0.86; 97.54% CI，0.65 - 1.13; P = 0.219）。在接受凡德他尼治疗的患者中，观察到客观缓解率（19% vs8%; P <0.001）和症状恶化时间（HR，0.71; P = 0.0052;中位数，凡德他尼组为18.1周，安慰剂组为12.1周）的统计学显著改善。在培美曲塞的基础上添加凡德他尼会增加一些不良事件的发生率，包括皮疹、腹泻和高血压，同时显示恶心、呕吐、贫血、疲劳和虚弱的发生率降低，而培美曲塞的剂量强度没有降低。结论这项研究没有达到主要终点，即凡德他尼加培美曲塞与安慰剂加培美曲塞相比，PFS延长具有统计学意义。与安慰剂组相比，凡德他尼联合治疗组的客观缓解率显著更高，至肺癌症状恶化的时间显著延迟，并且在该患者人群中具有可接受的安全性特征。J Clin Oncol 29：1067-1074. (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 randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non-small-cell lung cancer.Patients and MethodsPatients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments.ResultsThere was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed.ConclusionThis study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population. J Clin Oncol 29:1067-1074. (c) 2011 by American Society of Clinical Oncology