如何选择初始不可切除的结直肠癌肝转移患者一线全身治疗策略:CAIRO5研究结果解读  

How to Choose the First-Line Systemic Treatment Strategies for Patients with Initially Unresectable Colorectal Cancer Liver Metastases:Interpretation of CAIRO5 Study Results

作　　者：蔡奕波 谢丽 CAI Yibo;XIE Li(Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310022.China;Clinical Research Center,Shanghai JiaoTong University School of Medicine,Shanghai 200025,China)

机构地区：[1]浙江省肿瘤医院,中国科学院杭州医学研究所,浙江杭州310022 [2]上海交通大学医学院临床研究中心,上海200025

出　　处：《肿瘤学杂志》2023年第9期799-808,共10页Journal of Chinese Oncology

摘　　要：CAIRO5是一项开放标签、多中心、随机、对照Ⅲ期研究,旨在比较对于初始不可切除的结直肠癌肝转移(colorectal cancer liver metastases,CRLM)患者,目前临床常用的一线全身治疗策略的疗效及安全性。该研究在2014年11月13日至2022年1月31日期间在荷兰46个和比利时1个二/三级医疗中心进行。根据原发部位及基因状态进行分层随机分组,右侧原发性肿瘤部位或RAS或者BRAF^(V600E)突变肿瘤患者随机分配(1∶1)接受FOLFOX或FOLFIRI联合贝伐单抗(A组)或者FOLFOXIRI联合贝伐单抗(B组)。左侧肿瘤且RAS和BRAF^(V600E)野生型肿瘤患者随机分配(1∶1)接受FOLFOX或FOLFIRI联合贝伐单抗(C组)或者FOLFOX或FOLFIRI联合帕尼单抗(D组)。主要研究终点是ITT人群的无进展生存期。本研究共纳入530例初始不可切除的CRLM患者,其中A组148例(28%),B组146例(28%),C组118例(22%),D组118例(22%)。C组和D组因研究失败而提前关闭。右侧原发性肿瘤部位或者RAS或BRAF^(V600E)突变肿瘤患者中,与FOLFOX或FOLFIRI加贝伐单抗治疗组相比较,FOLFOXIRI联合贝伐单抗治疗组可以延长中位无进展生存期(10.6个月vs 9.0个月,P=0.032),降低CRLM患者的疾病进展或死亡风险23%。而在左侧肿瘤且RAS和BRAF^(V600E)野生型肿瘤患者中,FOLFOX或FOLFIRI联合贝伐单抗治疗组和FOLFOX或FOLFIRI联合帕尼单抗治疗组之间中位无进展生存期无统计学差异(10.8个月vs 10.4个月,P=0.46)。在安全性方面,FOLFOXIRI联合贝伐单抗治疗组严重不良事件(≥3级)明显高于FOLFOX或FOLFIRI加贝伐单抗治疗组(52%vs 31%),其中最常见的是中性粒细胞减少症,同时FOLFOXIRI联合贝伐单抗治疗组报告了7例与治疗相关死亡病例,显著高于其他治疗组。在左侧肿瘤且RAS和BRAF^(V600E)野生型肿瘤患者中,FOLFOX或FOLFIRI中加入帕尼单抗,相比较于贝伐单抗,并未显示临床获益,但与更高的严重不良事件(≥3级)发生率相关。CAIRO5研究结果提示,CAIRO-5 is an open-label,multi-center,randomized,controlled phaseⅢstudy designed to compare the efficacy and safety of currently most active first-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases(CRLM).The study was conducted in Dutch 46 and Belgian 1 secondary/tertiary centers between November 13,2014 and January 31,2022.Stratified randomization was performed according to the primary tumor site and gene status.Patients with right-sided primary tumor,or RAS or BRAF^(V600E)mutated tumors were randomly assigned(1∶1)to receive FOLFOX or FOLFIRI plus bevacizumab(group A)or FOLFOXIRI plus bevacizumab(group B).Patients with left-sided and RAS and BRAF^(V600E)wild-type tumors were randomly assigned(1∶1)to receive FOLFOX or FOLFIRI plus bevacizumab(group C)or FOLFOX or FOLFIRI plus panitumumab(group D).The primary outcome was progression-free survival in the intention-to-treat population.A total of 530 patients with initially unresectable CRLM were enrolled in this study,including 148 cases(28%)in group A,146 cases(28%)in group B,118 cases(22%)in group C,and 118 cases in group D(22%).Groups C and D were prematurely closed for futility.Among patients with right-sided primary tumor,or RAS or BRAF^(V600E)mutated tumors,treatment with FOLFOXIRI plus bevacizumab prolonged median progression-free survival compared with FOLFOX or FOLFIRI plus bevacizumab(10.6 months vs 9.0 months,P=0.032),reducing the risk of disease progression or death in patients with CRLM by 23%.For patients with left-sided,and RAS and BRAF^(V600E)wild-type tumors,there was no statistically significant difference in median progression-free survival between group C and group D(10.8 months vs 10.4 months,P=0.46).In terms of safety,the serious adverse events(grade≥3)in group B were significantly higher than those in group A(52%vs 31%).The most common grade 3~4 event was neutropenia.Remarkably,7 treatment-related deaths were reported in group B,which was significantly higher than in the other

关 键 词：结直肠癌肝转移 肿瘤部位 RAS/BRAF基因突变 治疗策略 

分 类 号：R735.3[医药卫生—肿瘤]