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Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study.帕博利珠单抗对比伊匹单抗用于晚期黑色素瘤(KEYNOTE-006):一项开放标签、多中心、随机、对照、III 期研究的 5 年随访后结果。
Lancet Oncol. 2019 Sep;20(9):1239-1251. doi: 10.1016/S1470-2045(19)30388-2. Epub 2019 Jul 22.
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Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006).帕博利珠单抗对比伊匹单抗用于晚期黑色素瘤:一项多中心、随机、开放标签的 3 期研究(KEYNOTE-006)的最终总生存结果。
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Lancet Oncol. 2016 Dec;17(12):1743-1754. doi: 10.1016/S1470-2045(16)30578-2. Epub 2016 Nov 16.

一线 BRAF/MEK 抑制剂与 BRAF 突变型晚期黑色素瘤患者的抗 PD-1 单药治疗:一项倾向评分匹配生存分析。

First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAF-mutant advanced melanoma patients: a propensity-matched survival analysis.

机构信息

Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden, 2333AA, The Netherlands.

Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam, 1081HZ, The Netherlands.

出版信息

Br J Cancer. 2021 Mar;124(7):1222-1230. doi: 10.1038/s41416-020-01229-1. Epub 2021 Jan 26.

DOI:10.1038/s41416-020-01229-1
PMID:33495600
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8007796/
Abstract

BACKGROUND

Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAF-mutant advanced melanoma. Until now, data are inconclusive on which therapy to use as first-line treatment. The aim of this study was to use propensity score matching to compare first-line anti-PD-1 monotherapy vs. BRAF/MEK inhibitors in advanced BRAF-mutant melanoma patients.

METHODS

We selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAF-mutation treated with first-line BRAF/MEK inhibitors or anti-PD-1 antibodies, registered in the Dutch Melanoma Treatment Registry. Patients were matched based on their propensity scores using the nearest neighbour and the optimal matching method.

RESULTS

Between 2014 and 2017, a total of 330 and 254 advanced melanoma patients received BRAF/MEK inhibitors and anti-PD-1 monotherapy as first-line systemic therapy. In the matched cohort, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year overall survival compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months (95% CI: 37.3-NE) vs. 19.8 months (95% CI: 16.7-24.3) and 65.4% (95% CI: 58.1-73.6) vs. 41.7% (95% CI: 34.2-51.0).

CONCLUSIONS

Our data suggest that in the matched BRAF-mutant advanced melanoma patients, anti-PD-1 monotherapy is the preferred first-line treatment in patients with relatively favourable patient and tumour characteristics.

摘要

背景

抗 PD-1 抗体和 BRAF/MEK 抑制剂是治疗 BRAF 突变型晚期黑色素瘤的两种主要系统治疗药物。到目前为止,哪种治疗方法作为一线治疗仍无定论。本研究旨在通过倾向评分匹配,比较晚期 BRAF 突变型黑色素瘤患者一线抗 PD-1 单药治疗与 BRAF/MEK 抑制剂治疗。

方法

我们选择了 2014 年至 2017 年间在荷兰黑色素瘤治疗登记处登记的接受一线 BRAF/MEK 抑制剂或抗 PD-1 抗体治疗的晚期黑色素瘤且已知存在 BRAF 突变的患者。采用最近邻和最佳匹配方法,根据倾向评分对患者进行匹配。

结果

2014 年至 2017 年间,共 330 例和 254 例晚期黑色素瘤患者分别接受 BRAF/MEK 抑制剂和抗 PD-1 单药作为一线全身治疗。在匹配队列中,接受抗 PD-1 抗体作为一线治疗的患者中位总生存期和 2 年总生存率均高于接受一线 BRAF/MEK 抑制剂治疗的患者,分别为 42.3 个月(95%CI:37.3-NE)和 19.8 个月(95%CI:16.7-24.3),65.4%(95%CI:58.1-73.6)和 41.7%(95%CI:34.2-51.0)。

结论

本研究数据表明,在匹配的 BRAF 突变型晚期黑色素瘤患者中,抗 PD-1 单药治疗可能是具有相对有利的患者和肿瘤特征患者的首选一线治疗方法。