恩考芬尼、西妥昔单抗与化疗用于BRAF突变型结直肠癌：一项随机3期试验

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

作者信息

Kopetz Scott, Yoshino Takayuki, Van Cutsem Eric, Eng Cathy, Kim Tae Won, Wasan Harpreet Singh, Desai Jayesh, Ciardiello Fortunato, Yaeger Rona, Maughan Timothy S, Beyzarov Elena, Zhang Xiaoxi, Ferrier Graham, Zhang Xiaosong, Tabernero Josep

机构信息

University of Texas MD Anderson Cancer Center, Houston, TX, USA.

National Cancer Center Hospital East, Kashiwa, Japan.

出版信息

Nat Med. 2025 Mar;31(3):901-908. doi: 10.1038/s41591-024-03443-3. Epub 2025 Jan 25.

DOI:10.1038/s41591-024-03443-3

PMID:39863775

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11922750/

Abstract

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403-4.253; 99.8% CI: 1.019-5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318-0.691; repeated CI: 0.166-1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421 .

摘要

基于BEACON 3期研究，恩考芬尼+西妥昔单抗（EC）被批准用于既往接受过治疗的BRAF V600E突变转移性结直肠癌（mCRC）。从历史上看，采用化疗方案一线治疗BRAF V600E突变mCRC的疗效有限。3期BREAKWATER研究在既往未接受过治疗的BRAF V600E mCRC患者中比较了EC+mFOLFOX6与标准治疗（SOC）。无进展生存期的双主要终点是事件驱动的；在数据截止时数据尚未成熟。BREAKWATER达到了客观缓解率的另一个双主要终点，显示客观缓解率有显著且具有临床意义的改善（EC+mFOLFOX6：60.9%；SOC：40.0%；优势比，2.443；95%置信区间（CI）：1.403-4.253；99.8%CI：1.019-5.855；单侧P = 0.0008）。中位缓解持续时间为13.9个月对11.1个月。在本次总生存期的首次中期分析中，风险比为0.47（95%CI：0.318-0.691；重复CI：0.166-1.322）。严重不良事件发生率分别为37.7%和34.6%。安全性特征与每种药物已知的特征一致。BREAKWATER表明，对于BRAF V600E mCRC患者，一线使用EC+mFOLFOX6相对于SOC的缓解率有显著提高且持久。ClinicalTrials.gov标识符：NCT04607421 。