encorafenib/西妥昔单抗联合或不联合 binimetinib 治疗 BRAF V600E 突变型转移性结直肠癌患者的疗效和安全性：一项 ACEO 真实世界多中心研究。
Efficacy and safety of the combination of encorafenib/cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: an AGEO real-world multicenter study.
机构信息
Department of Gastroenterology and Digestive Oncology, Paris-Cité University, Georges Pompidou European Hospital, SIRIC CARPEM, Paris, France.
Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
出版信息
ESMO Open. 2024 Sep;9(9):103696. doi: 10.1016/j.esmoop.2024.103696. Epub 2024 Sep 9.
BACKGROUND
The combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) after a prior systemic therapy. This study aims to describe the efficacy and safety of encorafenib/cetuximab +/- binimetinib in patients with BRAF V600E-mutated mCRC in a real-world setting.
PATIENTS AND METHODS
This retrospective study included patients with BRAF V600E-mutated mCRC who received this combination from January 2020 to June 2022 in 30 centers.
RESULTS
A total of 201 patients were included, with 55% of women, a median age of 62 years, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) >1 in 20% of cases. The main tumor characteristics were 60% of right-sided primary tumor, 11% of microsatellite instability/mismatch repair deficient phenotype, and liver and peritoneum being the two main metastatic sites (57% and 51%). Encorafenib/cetuximab +/- binimetinib was prescribed in the first, second, third, and beyond third line in 4%, 56%, 29%, and 11%, respectively, of cases, with the encorafenib/cetuximab/binimetinib combination for 21 patients (10%). With encorafenib/cetuximab treatment, 21% of patients experienced grade ≥3 adverse events (AEs), with each type of grade ≥3 AE observed in <5% of patients. The objective response rate was 32.2% and the disease control rate (DCR) was 71.2%. The median progression-free survival (PFS) was 4.5 months [95% confidence interval (CI) 3.9-5.4 months] and the median overall survival (OS) was 9.2 months (95% CI 7.8-10.8 months). In multivariable analysis, factors associated with a shorter PFS were synchronous metastases [hazard ratio (HR) 1.66, P = 0.04] and ECOG-PS >1 (HR 1.88, P = 0.007), and those associated with a shorter OS were the same factors (HR 1.71, P = 0.03 and HR 2.36, P < 0.001, respectively) in addition to treatment beyond the second line (HR 1.74, P = 0.003) and high carcinoembryonic antigen level (HR 1.72, P = 0.003).
CONCLUSION
This real-world study showed that in patients with BRAF V600E-mutated mCRC treated with encorafenib/cetuximab +/- binimetinib, efficacy and safety data confirm those reported in the BEACON registration trial. The main poor prognostic factors for this treatment are synchronous metastases and ECOG-PS >1.
背景
在先前接受过系统治疗的 BRAF V600E 突变转移性结直肠癌（mCRC）患者中，encorafenib 联合 cetuximab 已成为标准治疗方案。本研究旨在描述在真实环境中，接受 BRAF V600E 突变 mCRC 治疗的患者中，encorafenib/cetuximab +/- binimetinib 的疗效和安全性。
患者和方法
这是一项回顾性研究，纳入了 2020 年 1 月至 2022 年 6 月期间在 30 个中心接受该联合治疗的 BRAF V600E 突变 mCRC 患者。
结果
共纳入 201 例患者，其中 55%为女性，中位年龄为 62 岁，20%的患者 ECOG-PS >1。主要肿瘤特征包括：60%的原发肿瘤位于右侧，11%的为微卫星不稳定/错配修复缺陷表型，57%和 51%的主要转移部位为肝脏和腹膜。encorafenib/cetuximab +/- binimetinib 分别在 4%、56%、29%和 11%的病例中被处方为一线、二线、三线及以上治疗，21 例（10%）接受了 encorafenib/cetuximab/binimetinib 联合治疗。接受 encorafenib/cetuximab 治疗的患者中，21%发生了≥3 级不良事件（AE），每种≥3 级 AE 的发生率均<5%。客观缓解率为 32.2%，疾病控制率（DCR）为 71.2%。中位无进展生存期（PFS）为 4.5 个月（95%CI 3.9-5.4 个月），中位总生存期（OS）为 9.2 个月（95%CI 7.8-10.8 个月）。多变量分析显示，与较短 PFS 相关的因素包括同步转移（HR 1.66，P=0.04）和 ECOG-PS >1（HR 1.88，P=0.007），与较短 OS 相关的因素除了二线以上治疗（HR 1.74，P=0.003）和高癌胚抗原水平（HR 1.72，P=0.003）外，还包括相同的因素（HR 1.71，P=0.03 和 HR 2.36，P<0.001）。
结论
这项真实世界研究表明，在接受 encorafenib/cetuximab +/- binimetinib 治疗的 BRAF V600E 突变 mCRC 患者中，疗效和安全性数据与 BEACON 注册试验报告的数据一致。该治疗的主要预后不良因素是同步转移和 ECOG-PS >1。
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