Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada clinical trials group
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada clinical trials group
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DOI：
10.1200/jco.2006.07.9525
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发表时间：
2007-05-20
影响因子：
45.3
通讯作者：
Parulekar, Wendy
中科院分区：
文献类型：
--
作者：
Moore, Malcolm J.;Goldstein, David;Parulekar, Wendy
目的
晚期胰腺癌患者预后不良，自1996年吉西他滨应用以来，生存率没有改善。胰腺肿瘤常常过度表达人表皮生长因子受体1型（HER1/EGFR），这与更差的预后相关。我们研究了在不可切除、局部晚期或转移性胰腺癌患者中，在吉西他滨基础上加用HER1/EGFR靶向药物厄洛替尼的效果。
患者与方法
在一项双盲、国际多中心Ⅲ期试验中，患者按1∶1随机分组，接受标准吉西他滨加厄洛替尼（口服100或150mg/d）或吉西他滨加安慰剂。主要终点是总生存期。
结果
共有569例患者被随机分组。基于意向性治疗分析，厄洛替尼/吉西他滨组的总生存期显著延长，风险比（HR）为0.82（95%置信区间，0.69 - 0.99；P = 0.038，校正分层因素后；中位生存期6.24个月对5.91个月）。厄洛替尼加吉西他滨组的1年生存率也更高（23%对17%；P = 0.023）。厄洛替尼加吉西他滨组的无进展生存期显著更长，估计HR为0.77（95%置信区间，0.64 - 0.92；P = 0.004）。两组间的客观缓解率没有显著差异，尽管厄洛替尼组更多患者病情稳定。厄洛替尼加吉西他滨组某些不良事件发生率更高，但大多数为1级或2级。
结论
据我们所知，这项随机Ⅲ期试验首次证明在吉西他滨基础上加用任何药物可使晚期胰腺癌的生存期在统计学上显著改善。在此适应证中，厄洛替尼与吉西他滨联合的推荐剂量为100mg/d。
PurposePatients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival.ResultsA total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% Cl, 0.69 to 0.99; P=.038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P =.023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% Cl, 0.64 to 0.92; P =.004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2.ConclusionTo our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.