mFOLFOX7化疗方案联合卡瑞利珠单抗和阿帕替尼治疗CNLCⅢ期肝细胞癌有效性和安全性的前瞻性研究

mFOLFOX7 venous chemotherapy plus camrelizumab and apatinib for hepatocellular carcinoma in CNLC stageⅢ(VIC⁃TRIPLET):a prospective study

目的探索静脉mFOLFOX7化疗方案联合卡瑞利珠单抗和阿帕替尼在CNLCⅢ期肝细胞癌中的有效性及安全性(NCT05412589)。方法本研究为单臂、开放、前瞻性临床研究,计划入组35例未经治疗的CNLCⅢ期肝细胞癌患者。主要研究终点为基于RECIST 1.1标准评估的客观缓解率(ORR),次要研究终点包括:基于mRECIST标准评估的ORR,和基于RECIST 1.1标准和mRECIST标准评估的疾病控制率(DCR)、无进展生存时间(PFS),以及总生存时间(OS)、手术转化率、治疗相关不良反应(TRAE)等。结果收集并分析2021年4月至2023年4月期间符合入排标准并签署同意书入组的26例肝细胞癌患者资料。中位随访时间为13个月,ORR为61.5%(RECIST v1.1)和73.1%(mRECIST),临床缓解率为26.9%,病理完全缓解率为23.1%,DCR为96.2%,mPFS和mOS均尚未达到,均超过9个月。手术转化率为57.7%,均实现R0切除。TRAE≥3级不良事件发生率为50%。结论静脉mFOLFOX7化疗方案联合卡瑞利珠单抗和阿帕替尼是治疗CNLCⅢ期肝细胞癌的一种有效、安全、易行的策略,初步研究效果类似于FOLFOX⁃HAIC联合靶免治疗。

Objective The combination of anti⁃angiogenesis and immune checkpoint blockade showed promising outcomes for advanced HCC.Hepatic artery infusion chemotherapy(HAIC)combined with apatinib and camrelizumab could augment treatment efficacy in preliminary study.But HAIC had disadvantages such as technical limitations,expensive cost and poor patient comfort.In the present study,we aimed to investigate the efficacy and safety of Venous Infusion Chemotherapy(VIC)plus camrelizumab and apatinib for CNLC stageⅢHCC.Method This study is a single⁃arm,open,prospective clinical study planned to enroll 35 untreated patients with stage CNLCⅢhepatocellular carcinoma.Eligible pts received VIC(oxaliplatin 85 mg/m^(2),leucovorin 200 mg/m^(2),5⁃fluorouracil bolus 400 mg/m^(2)on day 1,and 5⁃fluorouracil infusion 2400 mg/m^(2)for 46 hours;q3w;6 cycles),combined with apatinib(250 mg qd)and camrelizumab(200 mg q3w).The primary study endpoints were objective response rate(ORR)assessed based on the RECIST 1.1 criteria,while the secondary study endpoints included:ORR assessed based on RECIST 1.1,mRECIST criteria,and disease control rate(DCR),progression⁃free survival time(PFS),overall survival time(OS),surgical conversion rate,adverse reactions(AE),etc.Results Data of 26 liver cancer patients who met the entry criteria and signed the consent form from April 2021 to April 2023 were collected and analyzed.The median follow⁃up was 13 months,ORR 61.5%(RECISTv1.1)and 73.1%(mRECIST),cCR rate 26.9%,pCR 23.1%,DCR 96.2%,and mPFS and mOS were not reached,both over 9 months.The surgical conversion rate was 57.7%,all achieving R0 resection.The incidence of treatment⁃related adverse effects(TRAE)grade 3 AEs was 50%.Conclusion The triplet treatment of VIC plus camrelizumab and apatinib showed promising antitumor activity and acceptable safety for CNLC stageⅢHCC,and the preliminary study effect is similar to that of FOLFOX⁃HAIC combined with camrelizumab and apatinib.Especially for patients with main portal vein cancer thrombus,the combined treatment scheme is worthy of clinical application.