背景:恩科拉非尼联合西妥昔单抗已成为BRAFV600E突变的转移性结直肠癌(mCRC)患者在之前的全身治疗后的治疗标准。本研究旨在描述在真实世界环境中,恩科拉非尼/西妥昔单抗+/-比尼美替尼在BRAFV600E突变mCRC患者中的疗效和安全性。
方法:这项回顾性研究纳入了2020年1月至2022年6月在30个中心接受BRAFV600E突变mCRC联合治疗的患者。
结果:共纳入201例患者,55%的女性,平均年龄为62岁,在20%的病例中,东部肿瘤协作组的表现状态(ECOG-PS)>1。主要肿瘤特征为60%的右侧原发肿瘤,11%的微卫星不稳定性/错配修复缺陷表型,肝脏和腹膜是两个主要的转移部位(57%和51%)。恩科拉菲尼/西妥昔单抗+/-比米替尼在第一次处方中,第二,第三,超过三线的4%,56%,29%,11%,分别,的情况下,恩科拉非尼/西妥昔单抗/比尼替尼联合治疗21例患者(10%)。使用恩科拉非尼/西妥昔单抗治疗,21%的患者出现3级以上不良事件(AE),在<5%的患者中观察到每种类型的≥3级AE。客观有效率为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%置信区间(CI)3.9-5.4个月],中位总生存期(OS)为9.2个月(95%CI7.8-10.8个月)。在多变量分析中,与较短PFS相关的因素是同步转移[风险比(HR)1.66,P=0.04]和ECOG-PS>1(HR1.88,P=0.007),与OS较短相关的因素是相同的因素(分别为HR1.71,P=0.03和HR2.36,P<0.001),除了二线治疗以外(HR1.74,P=0.003)和高癌胚抗原水平(HR1.72,P=0.003).
结论:这项现实世界研究表明,在接受恩科拉菲尼/西妥昔单抗+/-比尼替尼治疗的BRAFV600E突变mCRC患者中,疗效和安全性数据证实了BEACON注册试验中的报道.该治疗的主要不良预后因素是同步转移和ECOG-PS>1。
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.
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).
CONCLUSIONS: 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.