Melanoma Institute Australia and Westmead Hospital, University of Sydney, 40 Rocklands Road, North Sydney, New South Wales, Australia.
Eur J Cancer. 2013 Mar;49(5):1073-9. doi: 10.1016/j.ejca.2012.11.004. Epub 2012 Dec 10.
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.
BRAF 基因的激活突变发生在大约 50%的黑色素瘤中。超过 70%的 BRAF 突变是 V600E，10-30%是 V600K。有效的、选择性的 BRAF 抑制剂在 V600E 和 V600K BRAF 突变的黑色素瘤患者中显示出显著的临床益处。V600R 突变约占所有 BRAF 突变的 3-7%，而这种突变患者的 BRAF 抑制剂活性尚不清楚。我们通过同情用药项目，自 2011 年 7 月至 2012 年 10 月，用选择性 BRAF 抑制剂 dabrafenib（n=43）或 vemurafenib（n=2）治疗了 45 例 V600 突变黑色素瘤患者，包括 V600R 突变患者。整个患者群体的总反应率为 50%，无进展生存期为 5.5 个月。在可评估的 6 例 V600R BRAF 突变患者（n=9）中，有 5 例出现了客观缓解。我们的经验表明，V600R BRAF 突变的患者可以成功地用口服 BRAF 抑制剂治疗，并且分子诊断检测应包括这种类型的突变。
