Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma
Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma
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DOI：
10.1056/nejmoa1708539
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发表时间：
2017-11-09
影响因子：
158.5
通讯作者：
Kirkwood, J. M.
中科院分区：
文献类型：
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作者：
Long, G. V.;Hauschild, A.;Kirkwood, J. M.
BRAF抑制剂dabrafenib和MEK抑制剂trametinib联合治疗可提高BRAF V600突变晚期黑色素瘤患者的生存率。我们试图确定辅助性达拉非尼加曲美替尼是否会改善切除的、伴有BRAF V600突变的III期黑色素瘤患者的预后。患有BRAF V600 E或V600 K突变的III期黑色素瘤接受150 mg剂量的口服达拉非尼每日两次加2 mg剂量的曲美替尼每日一次（联合治疗，438例患者）或两个匹配的安慰剂片剂（432例患者）12个月。主要终点是无复发生存期。次要终点包括总生存率、无远处转移生存率、无复发率和安全性。在中位随访2.8年时，联合治疗组3年无复发生存率估计为58%，安慰剂组为39%（复发或死亡的风险比为0.47; 95%可信区间[CI]为0.39 - 0.58; P
BACKGROUNDCombination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations.METHODSIn this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety.RESULTSAt a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P