甲磺酸伊马替尼胶囊治疗C-KIT突变型晚期黑色素瘤的疗效及安全性观察

Efficacy and Safety of Imatinib Mesylate in Treatment of Advanced Melanoma with C-KIT Mutation

[目的]分析C-KIT突变型晚期黑色素瘤患者接受甲磺酸伊马替尼胶囊治疗的疗效及不良反应。[方法]C-KIT突变型晚期黑色素瘤患者接受甲磺酸伊马替尼胶囊靶向治疗（400mg每日1次）,直至疾病进展或无法耐受,观察临床疗效和安全性。[结果]17例患者接受甲磺酸伊马替尼治疗,中位随访时间31.7个月（2.9~46.1个月）,1年生存率88.0%,客观有效率（objective response rate,ORR）31.3%,疾病控制率（disease control rate,DCR）68.8%,5例部分缓解（partial response,PR）患者中,4例为11、13号外显子突变（80.0%）。中位无疾病进展时间（progression-free survival,PFS）3.0个月（95%CI：0.2~7.4）,治疗有效患者（PR＋SD）较无效患者（PD）者PFS、OS均明显延长（中位PFS 8.3个月vs 1.2个月,P〈0.001;中位OS 31.7个月vs 20.1个月,P=0.223）。不良反应主要包括水肿（35.2%）,腹泻（35.2%）,乏力（29.4%）,恶心、呕吐（17.6%）,皮疹（6.0%）。[结论]甲磺酸伊马替尼胶囊治疗C-KIT突变型晚期恶性黑色素瘤的临床疗效佳,且安全性良好。

[Objective] To evaluate the efficacy and safety of tyrosine kinase inhibitor imatinib mesylate in treatment for patients with advanced melanoma harboring C-KIT mutation. [Methods]Patients with advanced melanoma received a continuous dose of imatinib mesylate 400mg/d unless intolerable toxicities or disease progression occurred. The efficacy and adverse events were observed.[Results] Seventeen patients were eligible for evaluation,and the median follow-up time was 31.7 months（2.9~46.1 months）. One-year overall survival（OS） rate was 88.0%. The objective response rate（ORR） and disease control rate（DCR） were 31.3% and 68.8%,respectively. Among 5 partial response（PR）patients,4 cases with harbored mutations in exon 11 or 13. The median progression-free survival（PFS） was 3.0 months（95%CI：0.2~7.4）. PFS and OS was longer in patients who got PR or SD（stable disease） compared with those of progressive disease（PD）（median PFS 8.3 months vs 1.2 months,P0.001;median OS 31.7 months vs 21.0 months,P=0.223）. The main adverse events included edema（35.2%）,diarrhea（35.2%）,fatigue（29.4%）,nausea/vomiting（17.6%）and rash（6.0%）.[Conclusion] Imatinib is effective for patients of advanced melanoma harboring CKIT mutation,with tolerable adverse events.