Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer
Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer
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DOI：
10.1200/jco.2009.25.8707
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发表时间：
2010-03-10
影响因子：
45.3
通讯作者：
Badwe, Rajendra
中科院分区：
文献类型：
--
作者：
Burstein, Harold J.;Sun, Yan;Badwe, Rajendra
目的来那替尼是一种口服、不可逆的泛ErbB受体酪氨酸激酶抑制剂。来那替尼的疗效和安全性进行了评估，在两个队列的患者与晚期ErbB 2阳性乳腺癌患者和那些没有事先曲妥珠单抗治疗，在一个开放标签，多中心，II期trial.Patients和方法患者在两个队列（前曲妥珠单抗，n = 66;没有事先曲妥珠单抗，n = 70）接受口服来那替尼240毫克，每天一次。主要终点是16周的无进展生存（PFS）率为可评估的人口（前曲妥珠单抗，n = 63;没有前曲妥珠单抗，n = 64），作为评估的独立review.Results的16周PFS率为59%的患者与前曲妥珠单抗治疗和78%的患者与前曲妥珠单抗治疗。中位PFS分别为22.3周和39.6周。既往接受过曲妥珠单抗治疗的患者的客观缓解率为24%，曲妥珠单抗初治队列的客观缓解率为56%。最常见的不良反应是腹泻、恶心、呕吐和疲劳。腹泻是最常见的3 - 4级不良事件，发生于30%既往接受过曲妥珠单抗治疗的患者和13%既往未接受过曲妥珠单抗治疗的患者，分别导致29%和4%的患者剂量降低，但仅1例患者停药。没有来那替尼相关的，3级或4级心脏toxicitywerened.Conclusion口服来那替尼显示出实质性的临床活性，是合理的耐受性良好的重度预处理和曲妥珠单抗初治的晚期，ErbB 2阳性乳腺癌患者。腹泻是最常见的不良反应，但可通过抗真菌药物和剂量调整进行管理。
Purpose Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial.Patients and Methods Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review.Results The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naive cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported.Conclusion Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naive patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.