[评论]西妥昔单抗联合FOLFOXIRI与西妥昔单抗联合FOLFOX作为初始无法切除的RAS/BRAF野生型结直肠癌肝转移患者的转化治疗方案(TRICE试验):一项随机对照试验  

[Comment]Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases(TRICE trial):a randomized controlled trial

作　　者：张荣欣[1] Zhang Rongxin

机构地区：[1]中山大学肿瘤防治中心结直肠科,广东广州510060

出　　处：《结直肠肛门外科》2024年第4期483-485,共3页Journal of Colorectal & Anal Surgery

摘　　要：背景目前尚不清楚强化的化疗方案与抗EGFR单抗联合治疗是否可以为最初无法切除的RAS/BRAF野生型结直肠癌患者带来更好的临床结果。为此,在本研究中我们对西妥昔单抗联合FOLFOXIRI与西妥昔单抗联合FOLFOX作为转化方案(即肿瘤从无法切除到可切除)对初始无法切除的结直肠癌肝转移患者的疗效和安全性进行比较。方法和结果这项开放标签、随机临床试验于2018年4月至2022年12月在中国7家医疗中心开展,招募了146例初期无法行肿瘤切除术的RAS/BRAF野生型结直肠癌肝转移患者。采用分层区组随机化方法将患者(1∶1)分配到西妥昔单抗联合FOLFOXIRI组(三药组,n=72)或西妥昔单抗联合FOLFOX组(双药组,n=74)。分层因素包括肿瘤位置(左半结肠vs.右半结肠)和可切除性(技术上不可切除vs.转移瘤≥5个)。主要研究终点是客观缓解率。次要研究终点包括肿瘤缓解深度中位数、早期肿瘤缩小率、R0切除率、无进展生存期、总生存期(分析时未成熟)和安全性。影像学肿瘤评估由不知晓组别分配的影像科医师进行。主要疗效分析基于意向治疗人群,而安全性分析则针对至少接受过一线化疗的患者进行。共有14例患者(9.6%)失访(双药组9例,三药组5例)。调整分层因素后,客观缓解率相当,三药组和双药组的客观缓解率分别为84.7%和79.7%(OR=0.70,95%CI为0.30~1.67,P=0.42)。此外,三药组和双药组的早期肿瘤缩小率没有显著差异【80.6%(58/72)vs.77.0%(57/74),OR=0.82,95%CI为0.37~1.83,P=0.63)】。虽然三药组的肿瘤缓解深度中位数为59.6%(IQR为50.0%~69.7%),双药组的肿瘤缓解深度中位数为55.0%(IQR为42.8%~63.8%),两组比较差异有统计学意义(P=0.039)。无论是否接受射频消融/立体定向放射治疗,三药组的R0/R1切除率均为54.2%(39/72),双药组为52.7%(39/74)。中位随访时间为26.2个月(IQR为12.8~40.5个月),三药组的中位无进展生存期为11.8个月,�Background It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer(CRC)patients with initially unresectable colorectal liver metastases(CRLM).To that end,we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI(triplet arm)versus cetuximab plus FOLFOX(doublet arm)as a conversion regimen(i.e.,unresectable to resectable)in CRC patients with unresectable CRLM.Methods and findings This open-label,randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China,enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM.A stratified blocked randomization method was utilized to assign patients(1∶1)to either the cetuximab plus FOLFOXIRI(n=72)or cetuximab plus FOLFOX(n=74)treatment arms.Stratification factors were tumor location(left versus right)and resectability(technically unresectable versus≥5 metastases).The primary outcome was the objective response rate(ORR).Secondary outcomes included the median depth of tumor response(DpR),early tumor shrinkage(ETS),R0 resection rate,progression-free survival(PFS),overall survival(not mature at the time of analysis),and safety profile.Radiological tumor evaluations were conducted by radiologists blinded to the group allocation.Primary efficacy analyses were conducted based on the intention-to-treat population,while safety analyses were performed on patients who received at least 1 line of chemotherapy.A total of 14 patients(9.6%)were lost to follow-up(9 in the doublet arm and 5 in the triplet arm).The ORR was comparable following adjustment for stratification factors,with 84.7%versus 79.7%in the triplet and doublet arms,respectively[OR,0.70;95%confidence intervals(CI),0.30-1.67;Chi-square P=0.42].Moreover,the ETS rate showed no significant difference between the triplet and doublet arms[80.6%(58/72)versus 77.0%(57/74);OR,0.82;95%CI 0.37-1.83,Chi-square

关 键 词：结直肠癌 RAS/BRAF 肝转移 

分 类 号：R735.3[医药卫生—肿瘤]