Department of Health Research Methods, Evidence, and Impact, McMaster University, Room 2C16, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Room 2C16, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada; Department of Oncology, McMaster University, Juravinski Cancer Centre, 699 Concession Street, 3rd Floor, Room 3-66, Hamilton, Ontario L8V 5C2, Canada.
Cancer Treat Rev. 2019 Mar;74:43-48. doi: 10.1016/j.ctrv.2019.02.001. Epub 2019 Feb 16.
The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of head-to-head evidence comparing targeted and immunotherapies. The purpose of this study is to conduct a network meta-analysis (NMA) in previously untreated, BRAF-mutated melanoma patients and estimate the relative efficacy of systemic therapies for this patient population at the treatment level.
The literature review included searches of MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) to November 2018. Randomized controlled trials of previously untreated patients with advanced melanoma were eligible if at least one intervention was either a targeted or immune therapy. Relative treatment effects were estimated by fixed effect Bayesian NMAs on progression-free survival (PFS) and overall survival (OS), based on the hazard ratio.
Combination dabrafenib with trametinib (HR 0.22 [95% CrI 0.17, 0.28] vs dacarbazine) and combination vemurafenib with cobimetinib (HR 0.22 [95% CrI 0.17, 0.29] vs dacarbazine) were likely to rank as the most favorable treatment options for PFS, while combination nivolumab with ipilimumab was likely to be the most efficacious in terms of OS (HR 0.33 [0.24, 0.47] vs dacarbazine).
The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma. However, as few trials informed each treatment comparison, research is needed to further refine our understanding of this complex and rapidly evolving treatment landscape.
对于转移性 BRAF 突变型黑色素瘤患者，治疗选择范围广泛，涵盖了多种治疗类别。然而，目前缺乏头对头比较靶向治疗和免疫治疗的证据。本研究旨在对未经治疗的 BRAF 突变型黑色素瘤患者进行网络荟萃分析（NMA），并在治疗水平上估计该患者人群接受系统治疗的相对疗效。
文献检索包括对 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册库（CENTRAL）的检索，检索时间截至 2018 年 11 月。如果至少有一种干预措施是靶向或免疫治疗，则将未经治疗的晚期黑色素瘤患者的随机对照试验纳入研究。基于风险比，通过固定效应贝叶斯 NMA 估计无进展生存期（PFS）和总生存期（OS）的相对治疗效果。
达拉非尼联合曲美替尼（HR 0.22 [95% CrI 0.17, 0.28] 与达卡巴嗪）和维莫非尼联合考比替尼（HR 0.22 [95% CrI 0.17, 0.29] 与达卡巴嗪）可能是 PFS 最有利的治疗选择，而纳武单抗联合伊匹单抗可能是 OS 最有效的治疗选择（HR 0.33 [0.24, 0.47] 与达卡巴嗪）。
这些发现强调了 PD-1 联合 CTLA-4 抑制剂和 BRAF 联合 MEK 抑制剂联合治疗晚期黑色素瘤的疗效。然而，由于很少有试验能够提供每种治疗比较的信息，因此需要开展研究以进一步深入了解这一复杂且快速发展的治疗领域。
