Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification
Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification
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甲磺酸伊马替尼治疗携带 c-Kit 突变或扩增的转移性黑色素瘤患者的 II 期、开放标签、单臂试验
DOI：
10.1200/jco.2010.33.9275
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发表时间：
2011-07-20
影响因子：
45.3
通讯作者：
Qin, Shukui
中科院分区：
文献类型：
--
作者：
Guo, Jun;Si, Lu;Qin, Shukui
目的黑色素瘤存在c-Kit基因异常。我们测试了酪氨酸激酶抑制剂伊马替尼在具有c-Kit突变或扩增的转移性黑色素瘤患者中的有效性。每个患者接受连续剂量的伊马替尼400 mg/d，除非出现无法忍受的毒性或疾病进展。15例病情进展的患者被允许将剂量增加到800 mg/d。结果43例患者符合评估条件，中位随访时间为12.0个月。中位无进展生存期(PFS)为3.5个月，6个月PFS率为36.6%。总的疾病控制率为53.5%，其中部分缓解(PR)10例(23.3%，95%CI，10.2%~36.4%)，稳定13例(30.2%，95%CI，16.0%~44.4%)。肿瘤消退18例(41.9%)。值得注意的是，10个PR中有9个发生在外显子11或13突变的患者中，1年总生存率为51.0%。PR或SD对疾病进展的中位PFS和OS时间分别为9.0个月和1.5个月(P<；.001)和15.0个月和9.0个月(P=.036)。伊马替尼400 mg/d耐受性良好，在剂量增至800 mg/d的15例患者中仅1例获得SD。结论伊马替尼对存在c-Kit基因突变的转移性黑色素瘤患者具有显著的活性，总有效率为23.3%。增加到800毫克/天并不能恢复疾病控制。J Clin Oncol29：2904-2909。(C)2011年美国临床肿瘤学会
PurposeMelanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications.Patients and MethodsForty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d.ResultsForty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P < .001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD.ConclusionImatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control. J Clin Oncol 29:2904-2909. (C) 2011 by American Society of Clinical Oncology