背景:在亚洲人群中约15%的恶性黑色素瘤患者中发现了c-KIT突变。Regorafenib,口服多激酶抑制剂,对野生型和突变型KIT都有作用。
目标:这种多机构,第二阶段,单臂研究旨在评估瑞戈非尼对携带c-KIT突变的转移性恶性黑色素瘤的疗效.
方法:转移性黑色素瘤患者c-KIT突变阳性,在至少一线全身治疗后进展,都被套牢了.患者接受口服瑞戈非尼160mg,每日一次,持续3周(4周周期)。主要终点是疾病控制率(DCR),次要终点是安全性,总反应率(ORR),无进展生存期(PFS),总生存率(OS)。
结果:总计,23例患者入组。c-KIT突变常发生在外显子11(14/23,60.9%),其次是外显子13、17和9/5(21.7%),5(21.7%),和2名(8.7%)病人,分别。8周时的DCR为73.9%,2名患者(8.7%)达到完全缓解,5(21.7%)达到部分反应,10人(43.5%)病情稳定。ORR为30.4%(7/23)。中位随访期为15.7个月(95%置信区间[CI],9.6-21.3),中位OS和PFS分别为21.5个月(95%CI,15.1-27.9)和7.1个月(95%CI,5.0-9.2),分别。选定患者的循环肿瘤DNA分析显示,c-KIT与基于组织的肿瘤突变谱具有很高的相关性(85.7%)。最常见的不良事件(AE)是皮肤反应,包括掌足红感觉障碍(52.2%),39.1%(9/23)的患者报告了3级AE。
结论:Regorafenib在二线或后期治疗中在携带c-KIT突变的转移性黑色素瘤患者中表现出显著的活性。
BACKGROUND: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT.
OBJECTIVE: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations.
METHODS: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enroled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
RESULTS: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.7 months (95% confidence interval [CI], 9.6-21.3), and median OS and PFS were 21.5 months (95% CI, 15.1-27.9) and 7.1 months (95% CI, 5.0-9.2), respectively. Circulating tumour DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumour mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients.
CONCLUSIONS: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harbouring c-KIT mutations.