Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib
Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib
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DOI：
10.1200/jco.2015.62.9345
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发表时间：
2016-03-10
影响因子：
45.3
通讯作者：
Flaherty, Keith T.
中科院分区：
文献类型：
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作者：
Long, Georgina V.;Weber, Jeffrey S.;Flaherty, Keith T.
目的报道BRAF V600基因突变阳性转移性黑色素瘤患者在一期和二期研究中接受达普拉非尼联合曲美替尼治疗的初治患者和长期有效的患者的总体生存率(OS)和临床特征。方法从非随机分配的队列(B组)和随机分配的C组(C组)中，分别对接受DRAF抑制剂的初治患者(150/2组)和随机分配的队列(C部分)进行无进展和OS分析。结果在150/2组(n=78)中，B部分(n=24)和C部分(n=54)的1、2、3年无进展生存率分别为44%、22%、18%和41%、25%、21%。B组和C组的中位OS分别为27.4个月和25个月，1、2、3年OS分别为72%、60%和47%，C组分别为80%、51%和38%。生存期延长与转移少于3个器官和基线乳酸脱氢酶降低有关。在基线乳酸脱氢酶正常的患者中，3年的生存率为62%，在完全应答的患者中，3年的生存率为63%。结论达普拉非尼联合曲美替尼治疗BRAF V600突变阳性转移性黑色素瘤的初治患者的中位OS超过2年，3年时约有20%的患者没有进展。在基线状态下，预后特征良好的患者会出现持久的反应，这可能是可预测的。(C)2016年度美国临床肿瘤学会
PurposeTo report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation-positive metastatic melanoma.MethodsBRAF inhibitor-naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non-randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS.ResultsFor BRAF inhibitor-naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response.ConclusionDabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive. (C) 2016 by American Society of Clinical Oncology