BRAF inhibitor activity in V600R metastatic melanoma
BRAF inhibitor activity in V600R metastatic melanoma
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DOI：
10.1016/j.ejca.2012.11.004
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发表时间：
2013-03-01
影响因子：
8.4
通讯作者：
Long, Georgina V.
中科院分区：
文献类型：
--
作者：
Klein, Oliver;Clements, Arthur;Long, Georgina V.
大约 50% 的黑色素瘤中会发生 BRAF 基因的激活突变。超过 70% 的 BRAF 突变是 V600E，10-30% 是 V600K。强效、选择性 BRAF 抑制剂已在 V600E 和 V600K BRAF 突变黑色素瘤患者中表现出显着的临床益处。 V600R 突变约占所有 BRAF 突变的 3-7%，并且 BRAF 抑制剂在具有该突变的患者中的活性尚不清楚。 2011 年 7 月至 2012 年 10 月期间，我们通过富有同情心的访问计划，使用选择性 BRAF 抑制剂达拉非尼 (n = 43) 或维莫非尼 (n = 2) 治疗了 45 名 V600 突变黑色素瘤患者，其中包括 V600R 突变患者。整个人群的总体缓解率为 50%，无进展生存期为 5.5 个月。在 6 名可评估的 V600R BRAF 突变患者 (n = 9) 中观察到 5 种客观缓解。我们的经验表明，具有 V600R BRAF 突变的患者可以通过口服 BRAF 抑制剂成功治疗，并且分子诊断分析应包括检测此类突变。 (C) 2012 Elsevier Ltd. 保留所有权利。
Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K. Potent and selective BRAF inhibitors have demonstrated significant clinical benefits in patients with V600E and V600K BRAF-mutated melanoma. V600R mutations constitute approximately 3-7% of all BRAF mutations and the activity of BRAF inhibitors in patients with this mutation is unknown. We have treated 45 patients with V600 mutated melanoma including patients with V600R mutation between July 2011 and October 2012 with the selective BRAF inhibitor dabrafenib (n = 43) or vemurafenib (n = 2) via a compassionate access programme. The overall response rate was 50% for the whole population with a progression-free survival of 5.5 months. Five objective responses were seen in six assessable patients with V600R BRAF mutation (n = 9). Our experience suggests that patients with V600R BRAF mutations can be treated successfully with oral BRAF inhibitors, and molecular diagnostic assays should include detection of this type of mutation. (C) 2012 Elsevier Ltd. All rights reserved.