晚期BRAF突变结直肠癌的真实世界治疗现状分析

Analysis of the real-world treatment status of treatment of BRAF mutations in advanced colorectal cancer in the real world

目的探索真实世界中BRAF基因突变晚期结直肠癌治疗中的实际临床应用情况与疗效分析。方法回顾性分析2019-09-01-2021-12-30就诊于河南省肿瘤医院并确诊为BRAF基因突变的60例晚期结直肠癌患者临床资料。纳入患者根据用药情况分为3药联合化疗组[9例;FOLFOXIRI(氟尿嘧啶/亚叶酸钙、奥沙利铂和盐酸伊立替康)+贝伐珠单抗]、2药联合化疗组[48例;以氟尿嘧啶类药物为基础联合奥沙利铂或盐酸伊立替康+贝伐珠单抗]以及免疫治疗组[3例;使用程序性死亡受体1(PD-1)单抗]。42例(70.00%)患者进入二线治疗,二线治疗采用西妥昔单抗+BRAF抑制剂+MEK抑制剂(靶向组,19例)或盐酸伊立替康+氟尿嘧啶+贝伐珠单抗(化疗组,23例)。计数资料采用n(%)表示,χ^(2)检验或Fisher精确法比较不同治疗方案的疗效。生存分析采用Kaplan-Meier法,log-rank检验比较组间差异,多因素Cox比例风险回归分析探讨预后影响因素。结果3药联合与2药联合化疗组客观缓解率(ORR)分别为22.22%和8.33%,χ^(2)=0.428,P=0.513;疾病控制率(DCR)分别为66.67%和52.08%,χ^(2)=0.195,P=0.659;无进展生存期(PFS)分别为9.50和6.50个月,χ^(2)=8.087,P=0.005;总生存期(OS)分别为15.83和11.07个月,χ^(2)=0.523,P=0.470。靶向组和化疗组ORR分别为21.10%和8.70%,χ^(2)=1.302,P=0.384;DCR分别为63.20%和30.43%,χ^(2)=4.500,P=0.034;PFS分别为5.73和4.07个月,χ^(2)=8.833,P=0.003;OS分别为6.33和5.30个月,χ^(2)=0.796,P=0.372。多因素Cox回归分析显示,性别、分化程度及是否远处淋巴结转移是OS独立影响因素,均P<0.05。结论BRAF突变的晚期结直肠癌一线治疗中,不能耐受FOLFOXIRI者,氟尿嘧啶类联合奥沙利铂或盐酸伊立替康是可选择治疗方案;二线治疗中西妥昔+BRAF抑制剂+MEK抑制剂效果较佳。

Objective To explore the clinical application and efficacy of advanced colorectal cancer with V-raf murine sarcoma viral oncogene homolog(BRAF)gene mutations in the real world.Methods Retrospective analysis was conducted on the clinical data of 60 patients with advanced colorectal cancer diagnosed with BRAF-mutation who attended Henan Provincial Cancer Hospital from September 1,2019,to December 30,2021.The included patients.based on medication,were divided into a 3-agent combination chemotherapy groupE[n=9;FOLFOXIRI(fluorouracil/calcium folinic acid,oxaliplatin,and irinotecan hydrochloride)+bevacizumab],a 2-agent combination chemotherapy groupL[n=48;2-agent chemotherapy regimen based on fluorouracil analogs in combination with oxaliplatin or irinotecan hydrochloride+bevacizumab],and an immunotherapy groupE[n=3;patients using programmed death receptor 1(PD-1)]Forty-two patients(70.00%)entered the second-line treatment with cetuximab+BRAF inhibitor+MEK inhibitor(targeted group,n=19)or irinotecan hydrochloride+fluorouracil+bevacizumab(chemotherapy group,n=23).Count data were expressed as n(%),and the x test or Fishers exact method was used to compare the efficacy of different treatment options in each line.Survival analysis was performed using the Kaplan-Meier method,Log-rank test was used to compare the differences between groups,and multivariate Cox proportional hazards regression analysis was performed to explore the prognostic factors.Results The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)were 22.22%us 8.33%(χ^(2)=0.428,P=0.513),66.67%us 52.08%(χ^(2)=0.195,P=0.659),9.50 months us 6.50 months(χ^(2)=8.087,P=0.005),15.83 months us 11.07 months(χ^(2)=0.523,P=0.470)for the 3-agent combination chemotherapy group and 2-agent combination chemotherapy group,respectively.The ORR,DCR,PFS,OS of the 2 groups were 21.10%us 8.70%(χ^(2)=1.302,P=0.384),63.20%us 30.43%(χ^(2)=4.500,P=0.034),5.73 months us 4.07 months(χ^(2)=8.833,P=0.003),6.33 months vs 5.30 months(χ^(2)=0.796,P=0.372)for the targeted and chemotherapy groups defined by this model,respectively.Multifactorial Cox regression analysis showed that gender,degree of differentiation and distant lymph node metastasis were independent factors for OS(P<005).Conclusion In the first-line treatment of advanced colorectal with BRAF mutation,fluorouracil combined with oxaliplatin or irinotecan is an alternative treatment option for those who cannot tolerate FOLFOXIRI;Cetuximab+BRAF inhibitor+MEK inhibitor is more effective in the second-line treatment.