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三药联合疗法治疗黑色素瘤——BRAF/MEK 抑制剂联合抗 PD-(L)1 抗体。

Triplet Therapy in Melanoma - Combined BRAF/MEK Inhibitors and Anti-PD-(L)1 Antibodies.

机构信息

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

出版信息

Curr Oncol Rep. 2022 Aug;24(8):1071-1079. doi: 10.1007/s11912-022-01243-x. Epub 2022 Apr 2.

DOI:10.1007/s11912-022-01243-x
PMID:35366166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9249697/
Abstract

PURPOSE OF REVIEW

We provide an updated review of clinical trials evaluating the combination of BRAF/MEK inhibitors with anti-PD-(L)1 therapy (triplet therapy) for patients with advanced BRAF-mutant melanoma, accompanied by a summary of the biological evidence supporting this combination.

RECENT FINDINGS

Resistance to BRAF/MEK inhibition and comparatively low response rates to immune checkpoint inhibitors remain clinical challenges in the treatment of melanoma. Preclinical data demonstrates that targeted therapy is immune-modulatory and synergises with immune checkpoint inhibition. Several randomised controlled trials have evaluated the combination of targeted therapy with immune checkpoint inhibition. Triplet therapy has shown improvements in progression-free survival and durability of response compared to BRAF/MEK inhibition alone; however, questions remain regarding the best clinical scenario for implementation of this regimen in the era of front-line immunotherapy.

摘要

目的综述

我们提供了对评估 BRAF/MEK 抑制剂联合抗 PD-(L)1 治疗（三联疗法）治疗晚期 BRAF 突变型黑色素瘤的临床试验的最新回顾，同时总结了支持这种联合治疗的生物学证据。

最近的发现

BRAF/MEK 抑制的耐药性以及对免疫检查点抑制剂的相对低反应率仍然是黑色素瘤治疗中的临床挑战。临床前数据表明，靶向治疗具有免疫调节作用，并与免疫检查点抑制协同作用。几项随机对照试验已经评估了靶向治疗联合免疫检查点抑制的效果。与单独使用 BRAF/MEK 抑制剂相比，三联疗法在无进展生存期和反应持久性方面均有改善；然而，在免疫治疗一线治疗时代，对于这种方案的最佳临床应用场景仍存在疑问。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d6c/9249697/9ad865a4e250/11912_2022_1243_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d6c/9249697/9ad865a4e250/11912_2022_1243_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d6c/9249697/9ad865a4e250/11912_2022_1243_Fig1_HTML.jpg

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