近日，海军医科大学长征医院臧远胜团队报道了晚期BRAF突变癌症的靶向治疗：系统综述和网络荟萃分析。该项研究成果发表在2025年11月19日出版的《英国医学杂志》上。

为了探讨基于靶向治疗的策略在晚期BRAF突变结直肠癌中的个体化和比较疗效及安全性，研究组在PubMed、Embase、Cochrane图书馆和ClinicalTrials.gov以及国际会议记录中检索从成立到2025年5月31日的标准临床试验和多中心、真实世界的研究，调查靶向治疗晚期BRAF突变结直肠癌的疗效和安全性，且少有一项临床结果值得关注。

主要终点是第一线和第二线或更二线设置的总生存率。次要终点包括无进展生存期、客观反应率、疾病控制率和≥3级不良事件。进行了单臂荟萃分析、成对荟萃分析和网络荟萃分析，以汇集总体生存率和无进展生存率的95%可信区间（CrIs）的风险比，以及客观缓解率、疾病控制率和不良事件的95%置信区间的比值比。累积排名曲线下的排名图和曲面（SUCRA）评估了网络荟萃分析中方案的相对优势。

共纳入了60项研究，涉及4633名晚期BRAF突变的癌症患者。汇总估计表明，患者可以从基于抗EGFR（表皮生长因子受体）/BRAF的方案中受益。双重化疗（DCT）-抗EGFR/BRAF与最佳总体生存率相关，与一线设置中的DCT抗VEGF（血管内皮生长因子）（风险比0.49，95%CrI 0.36至0.66）、三重化疗抗VEGF（0.51，0.33至0.80）和抗EGFR/BRAF（0.70，0.51至0.96）方案相比，具有显著益处。在所有一线靶向治疗策略中，化疗抗EGFR/BRAF在总体生存率（DCT抗EGFR/BRAF的SUCRA=0.94，单药化疗（SCT）-抗EGFR/BRAF为0.90）和无进展生存率（DCT-抗EGFR/BRAF为0.93，SCT抗EGFR/BRF为0.92）方面显示出显著的优势。在第二或以后的线设置中，与其他替代策略相比，抗EGFR/BRAF在添加或不添加额外抑制剂（抗MEK（丝裂原活化蛋白激酶）或抗PI3K（磷酸肌醇3-激酶））的情况下表现出更好的疗效，根据排名概率和SUCRA在研究终点中排名最高。

研究结果表明，对于晚期BRAF突变癌症的初步治疗，将双重化疗与抗EGFR/BRAF治疗相结合可提供最佳的生存益处。对于之前接受过治疗的患者，抗EGFR/BRAF方案（有或没有MEK抑制剂）是最有效和可耐受的选择。

附：英文原文

Title: Targeted therapy in advanced BRAF-mutated colorectal cancer: systematic review and network meta-analysis

Author: Bao-Dong Qin, Xiao-Dong Jiao, Zhan Wang, Ke Liu, Yan Ling, Ying Wu, Yuan-Sheng Zang

Issue&Volume: 2025/11/19

Abstract:

Objective To investigate the individual and comparative efficacy and safety of targeted therapy based strategies in advanced BRAF-mutated colorectal cancer.

Design Systematic review and network meta-analysis.

Data sources PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to 31 May 2025, and international conference proceedings.

Eligibility criteria for selecting studies Clinical trials and multicentre, real world studies investigating the efficacy and safety of targeted therapies for advanced BRAF-mutated colorectal cancer with at least one of the clinical outcomes of interest.

Data synthesis The primary endpoint was overall survival in the first line and second or later line settings. Secondary endpoints included progression-free survival, objective response rate, disease control rate, and grade ≥3 adverse events. Single arm meta-analysis, pairwise meta-analysis, and network meta-analysis were performed to pool hazard ratios with 95% credible intervals (CrIs) for overall survival and progression-free survival, and odds ratios with 95% CrIs for objective response rate, disease control rate, and adverse events. The rankogram and surface under the cumulative ranking curve (SUCRA) evaluated the relative superiority of regimens in the network meta-analysis.

Results 60 studies involving 4633 patients with advanced BRAF-mutated colorectal cancer were included. Pooled estimates indicated that patients could benefit from an anti-EGFR (epidermal growth factor receptor)/BRAF based regimen. Doublet chemotherapy (DCT)-anti-EGFR/BRAF was associated with the best overall survival, providing significant benefits compared with DCT-anti-VEGF (vascular endothelial growth factor) (hazard ratio 0.49, 95% CrI 0.36 to 0.66), triplet chemotherapy-anti-VEGF (0.51, 0.33 to 0.80), and anti-EGFR/BRAF (0.70, 0.51 to 0.96) regimens in the first line setting. Chemotherapy-anti-EGFR/BRAF showed significant superiority in overall survival (SUCRA=0.94 for DCT-anti-EGFR/BRAF, 0.90 for single agent chemotherapy (SCT)-anti-EGFR/BRAF) and progression-free survival (0.93 for DCT-anti-EGFR/BRAF and 0.92 for SCT-anti-EGFR/BRAF) among all first line targeted therapy strategies. In the second or later line setting, anti-EGFR/BRAF with or without an additional inhibitor (anti-MEK (mitogen-activated protein kinase kinase) or anti-PI3K (phosphoinositide 3-kinase)), exhibited better efficacy compared with other alternative strategies, ranking highest across study endpoints based on rank probability and SUCRA.

Conclusions For initial treatment of advanced BRAF-mutated colorectal cancer, combining doublet chemotherapy with anti-EGFR/BRAF therapy offers the best survival benefit. For patients who have had previous treatment, anti-EGFR/BRAF regimens (with or without a MEK inhibitor) are the most effective and tolerable options.

DOI: 10.1136/bmj-2025-086026

Source: https://www.bmj.com/content/391/bmj-2025-086026