Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma.

IF 96.2 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL New England Journal of Medicine Pub Date : 2024-11-07 Epub Date: 2024-06-19 DOI:10.1056/NEJMoa2404139
Georgina V Long, Axel Hauschild, Mario Santinami, John M Kirkwood, Victoria Atkinson, Mario Mandala, Barbara Merelli, Vanna Chiarion Sileni, Marta Nyakas, Andrew Haydon, Caroline Dutriaux, Caroline Robert, Laurent Mortier, Jacob Schachter, Dirk Schadendorf, Thierry Lesimple, Ruth Plummer, James Larkin, Monique Tan, Sachin Bajirao Adnaik, Paul Burgess, Tarveen Jandoo, Reinhard Dummer
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Abstract

Background: The 5-year results of this trial showed that adjuvant therapy with dabrafenib plus trametinib resulted in longer relapse-free survival and distant metastasis-free survival than placebo among patients with BRAF V600-mutated stage III melanoma. Longer-term data were needed, including data regarding overall survival.

Methods: We randomly assigned 870 patients with resected stage III melanoma with BRAF V600 mutations to receive 12 months of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Here, we report the final results of this trial, including results for overall survival, melanoma-specific survival, relapse-free survival, and distant metastasis-free survival.

Results: The median duration of follow-up was 8.33 years for dabrafenib plus trametinib and 6.87 years for placebo. Kaplan-Meier estimates for overall survival favored dabrafenib plus trametinib over placebo, although the benefit was not significant (hazard ratio for death, 0.80; 95% confidence interval [CI], 0.62 to 1.01; P = 0.06 by stratified log-rank test). A consistent survival benefit was seen across several prespecified subgroups, including the 792 patients with melanoma with a BRAF V600E mutation (hazard ratio for death, 0.75; 95% CI, 0.58 to 0.96). Relapse-free survival favored dabrafenib plus trametinib over placebo (hazard ratio for relapse or death, 0.52; 95% CI, 0.43 to 0.63), as did distant metastasis-free survival (hazard ratio for distant metastasis or death, 0.56; 95% CI, 0.44 to 0.71). No new safety signals were reported, a finding consistent with previous trial reports.

Conclusions: After nearly 10 years of follow-up, adjuvant therapy with dabrafenib plus trametinib was associated with better relapse-free survival and distant metastasis-free survival than placebo among patients with resected stage III melanoma. The analysis of overall survival showed that the risk of death was 20% lower with combination therapy than with placebo, but the benefit was not significant. Among patients with melanoma with a BRAF V600E mutation, the results suggest that the risk of death was 25% lower with combination therapy. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).

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达拉非尼加曲美替尼辅助治疗 III 期黑色素瘤的最终结果。
研究背景这项试验的5年结果显示,在BRAF V600突变的III期黑色素瘤患者中,达拉非尼加曲美替尼的辅助治疗比安慰剂能带来更长的无复发生存期和无远处转移生存期。我们需要更长期的数据,包括总生存期的数据:我们随机分配了870名切除的BRAF V600突变III期黑色素瘤患者,让他们接受为期12个月的达拉菲尼(150毫克,每天两次)加曲美替尼(2毫克,每天一次)或两种匹配的安慰剂治疗。在此,我们报告了这项试验的最终结果,包括总生存期、黑色素瘤特异性生存期、无复发生存期和无远处转移生存期的结果:达拉非尼加曲美替尼的中位随访时间为 8.33 年,安慰剂为 6.87 年。达拉非尼加曲美替尼的总生存期Kaplan-Meier估计值优于安慰剂,但获益并不显著(死亡危险比为0.80;95%置信区间[CI]为0.62至1.01;通过分层对数秩检验,P=0.06)。包括792名BRAF V600E基因突变的黑色素瘤患者在内的多个预设亚组的生存期都一致获益(死亡危险比为0.75;95% CI为0.58至0.96)。达拉非尼加曲美替尼的无复发生存期优于安慰剂(复发或死亡的危险比为0.52;95% CI为0.43至0.63),无远处转移生存期也是如此(远处转移或死亡的危险比为0.56;95% CI为0.44至0.71)。没有报告新的安全信号,这一结果与之前的试验报告一致:经过近10年的随访,在切除的III期黑色素瘤患者中,达拉非尼加曲美替尼辅助治疗的无复发生存期和无远处转移生存期均优于安慰剂。对总生存期的分析表明,联合疗法的死亡风险比安慰剂低20%,但获益并不显著。在BRAF V600E基因突变的黑色素瘤患者中,结果表明联合疗法的死亡风险降低了25%。(由葛兰素史克公司和诺华公司资助;COMBI-AD ClinicalTrials.gov 编号:NCT01682083;EudraCT 编号:2012-001266-15)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
New England Journal of Medicine
New England Journal of Medicine 医学-医学:内科
CiteScore
145.40
自引率
0.60%
发文量
1839
审稿时长
1 months
期刊介绍: The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
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