一线转移性结直肠癌中 BRAF V600E 突变：来自 ARCAD 数据库的个体患者数据分析。
BRAF V600E Mutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data From the ARCAD Database.
机构信息
Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
Department of Medical Oncology, Sorbonne University, Saint-Antoine Hospital, Paris, France.
出版信息
J Natl Cancer Inst. 2021 Oct 1;113(10):1386-1395. doi: 10.1093/jnci/djab042.
BACKGROUND
First-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed to assess the prognostic and predictive impact of BRAFmt on the efficacy of targeted therapies with first-line chemotherapy.
METHODS
Individual patient data from first-line RCTs with BRAF and KRAS status data in the ARCAD database were pooled. Progression-free survival and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Outcomes were compared between treatment groups that were concurrently randomly assigned whenever possible.
RESULTS
A total of 6391 patients from 10 RCTs were included: 573 BRAFmt (9.0%), 2059 KRASmt (32.2%), and 3759 double wild type (58.8%). BRAFmt mCRC patients experienced statistically significantly poorer OS than those with KRASmt (adjusted hazard ratio [HRadj] = 1.46, 95% confidence interval [CI] = 1.30 to 1.64) and patients with double wild-type tumors (HRadj = 2.14, 95% CI = 1.94 to 2.36). Anti-EGFR agents did not improve progression-free survival or OS of BRAFmt mCRC patients, based on 4 RCTs testing chemotherapy with or without anti-epidermal growth factor receptor (anti-EGFR) (HRadj = 0.96, 95% CI = 0.71 to 1.30; and HRadj = 0.85, 95% CI = 0.66 to 1.14, respectively).
CONCLUSIONS
Our data suggest that the addition of anti-EGFR agents to chemotherapy is ineffective as first-line treatment for BRAFmt mCRC patients.
背景
BRAFV600E 突变（BRAFmt）转移性结直肠癌（mCRC）患者的一线治疗策略主要依赖于随机对照试验（RCT）的亚组分析。我们旨在评估 BRAFmt 对一线化疗联合靶向治疗疗效的预后和预测影响。
方法
ARCAD 数据库中包含 BRAF 和 KRAS 状态数据的一线 RCT 的个体患者数据进行了汇总。使用 Kaplan-Meier 和 Cox 模型评估无进展生存期和总生存期（OS）。只要可能，同时随机分配治疗组时，对结局进行比较。
结果
共纳入来自 10 项 RCT 的 6391 例患者：573 例 BRAFmt（9.0%）、2059 例 KRASmt（32.2%）和 3759 例双野生型（58.8%）。BRAFmt mCRC 患者的 OS 明显差于 KRASmt（调整后的危险比 [HRadj] = 1.46，95%置信区间 [CI] = 1.30 至 1.64）和双野生型肿瘤（HRadj = 2.14，95% CI = 1.94 至 2.36）患者。基于 4 项测试化疗联合或不联合抗表皮生长因子受体（抗-EGFR）的 RCT，抗-EGFR 药物并未改善 BRAFmt mCRC 患者的无进展生存期或 OS（HRadj = 0.96，95% CI = 0.71 至 1.30；和 HRadj = 0.85，95% CI = 0.66 至 1.14）。
结论
我们的数据表明，抗-EGFR 药物联合化疗作为 BRAFmt mCRC 患者的一线治疗无效。
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