摘要
目的伊马替尼已经改变了c-Kit的晚期黑色素瘤的治疗模式,但在辅助治疗中尚无尝试。我们开展这项临床研究(NCT01782508),旨在比较伊马替尼和大剂量干扰素(HDI)在c-Kit突变的术后高危患者中的疗效及安全性。方法 48例存在c-Kit 9、11或13号外显子突变的高危黑色素瘤患者被纳入此项研究,并随机(1∶2)分入伊马替尼组(400 mg/d)或HDI组(15×106 U/m2 d1~d5/周×4周,之后9×106 U,每周3次×48周)。主要终点指标为无复发生存期(RFS),次要终点指标为无远处转移生存时间(DMFS)、总生存时间(OS)及耐受性。结果最常见的c-Kit突变为c-KitL576P(13/48)。截至2015年10月,HDI组中的中位RFS为29.8个月(95%CI 23.3~36.3个月),明显优于伊马替尼组(10.0个月;95%CI 0~20.0个月)(P=0.029)。在c-KitL576P突变的患者中观察到类似的趋势(P=0.005)(伊马替尼组仅4.8个月,而HDI组达34.2个月)。两组患者的预计OS相似(P=0.43)。在HDI组中记录到更多的3~4度不良反应。结论在此项研究中,伊马替尼与HDI相比并未延长c-Kit突变高危黑色素瘤患者的RFS。伊马替尼可能不适合被推荐单独用于c-Kit突变高危黑色素瘤患者的辅助治疗。
Objective Imatinib has changed the treatment paradigm for metastatic melanoma with c-Kit aberrations. However, it has not been trailed whether imatinib could be used as adjuvant therapy for melanomas. We conducted a randomized phase Ⅱ clinical trial(NCT01782508) in high-risk melanoma patients bearing c-Kit mutations to compare the efficacy and safety of imatinib with high-dose IFN-α2b(HDI). Methods Forty-eight high-risk melanoma patients(stage Ⅱb-Ⅲc) with c-Kit mutations in exons 9, 11 or 13 after surgery without prior systemic therapy were randomized(ratio of 1∶2) to imatinib(400 mg daily) or HDI(15×106 Unit/m2 d1-5/week×4 weeks plus 9×106 Unit, 3 times a week×48 weeks) arm. The primary endpoint was recurrence-free survival(RFS), and the secondary endpoints were distant metastasis-free survival(DMFS), overall survival(OS) and tolerability. Results The most common c-Kit mutation in patients was c-KitL576P(13/48). By October 2015, the median RFS of patients in HDI arm was 29.8 months(95% CI: 23.3-36.3 months), which was significantly(P=0.029) superior to that in imatinib arm(10.0 months; 95% CI: 0-20.0 months). Similar trend of RFS(P=0.005) was observed in patients harboring c-KitL576 P mutation(4.8 months in imatinib arm versus 34.2 months in HDI arm). The estimated median OS was similar in both arms(P=0.43). More Grade 3/4 toxicities were recorded in the HDI arm. Conclusions Imatinib could not prolong RFS when compared with HDI as adjuvant therapy for high-risk melanoma patients with c-Kit mutations. Imatinib alone is not suitable for recommendation as adjuvant therapy for the high-risk melanoma patients with c-Kit mutations.
引文
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