Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Cancer. 2011 Oct 15;117(20):4633-41. doi: 10.1002/cncr.26120. Epub 2011 Mar 31.
Patients with gastrointestinal stromal tumors (GISTs) resistant to both imatinib and sunitinib have a poor prognosis and few therapeutic options. In this study, the efficacy and safety of nilotinib (AMN107) as a third-line therapy for patients with GISTs was evaluated.
A single-arm, open-label trial was conducted in 8 Japanese hospitals. The key eligibility criteria included resistance or intolerance to both imatinib and sunitinib treatment. The primary endpoint was disease control rate, defined as the percentage of patients with complete response, partial response (PR), or stable disease (SD) lasting 24 weeks or longer.
Thirty-five patients were enrolled and treated with nilotinib 400 mg twice daily, which generally was well tolerated. Disease control rate at Week 24 was 29% (90% confidence interval, 16.4%-43.6%). The median progression-free survival was 113 days, and the median overall survival was 310 days. The objective response rate was 3%, comprising 1 PR in a patient with a GIST possessing both a KIT exon 11 mutation, and an imatinib-resistant and sunitinib-resistant KIT exon 17 mutation. Twenty-three (66%) patients had SD (≥6 weeks) as the best response.
These results suggest that nilotinib is generally well tolerated and has encouraging antitumor activity in patients with GIST who failed both imatinib and sunitinib.
对伊马替尼和舒尼替尼均耐药的胃肠道间质瘤（GIST）患者预后较差，治疗选择有限。本研究评估了尼洛替尼（AMN107）作为三线治疗 GIST 患者的疗效和安全性。
在 8 家日本医院进行了一项单臂、开放标签试验。主要入选标准包括对伊马替尼和舒尼替尼治疗耐药或不耐受。主要终点为疾病控制率，定义为完全缓解、部分缓解（PR）或稳定疾病（SD）持续 24 周或更长时间的患者比例。
35 例患者接受尼洛替尼 400 mg 每日两次治疗，一般耐受性良好。24 周时疾病控制率为 29%（90%置信区间，16.4%-43.6%）。无进展生存期的中位数为 113 天，总生存期的中位数为 310 天。客观缓解率为 3%，包括 1 例 KIT 外显子 11 突变且存在伊马替尼耐药和舒尼替尼耐药 KIT 外显子 17 突变的 GIST 患者获得 PR。23 例（66%）患者的最佳缓解为 SD（≥6 周）。
这些结果表明，尼洛替尼总体耐受性良好，对伊马替尼和舒尼替尼均耐药的 GIST 患者具有令人鼓舞的抗肿瘤活性。
