甲苯磺酸多纳非尼联合经肝动脉栓塞化疗(TACE)及卡瑞利珠单抗转化治疗初始不可切除的肝细胞癌:一项前瞻性、单臂、单中心Ⅱ期临床试验  

Donafenib combined with transarterial chemoembolization (TACE) and camrelizumab as conversion therapy for initial unresectable hepatocellular carcinoma (HCC): a prospective, single-arm, single center, phase Ⅱ clinical study

作　　者：曹亚娟[1] 张雪斌[2] 史炯[3] 唐敏[4] 程春晓 余德才[1] CAO Yajuan;ZHANG Xuebin;SHI Jiong;TANG Min;CHENG Chunxiao;YU Decai(Department of Hepatobiliary and Transplantation Surgery,General Surgery,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院普通外科肝胆与肝移植外科,南京210008 [2]南京大学医学院附属鼓楼医院介入科,210008 [3]南京大学医学院附属鼓楼医院病理科,210008 [4]南京大学医学院附属鼓楼医院影像科,210008

出　　处：《临床肿瘤学杂志》2023年第6期481-487,共7页Chinese Clinical Oncology

基　　金：国家自然科学基金青年科学基金资助项目(82103453)。

摘　　要：目的 评估多纳非尼联合TACE及卡瑞利珠单抗转化治疗初始不可切除肝细胞癌(HCC)的有效性和安全性。方法 设计和开展一项前瞻性、单臂、单中心的Ⅱ期临床试验。本研究共纳入20例未接受系统治疗的初始不可切除HCC受试者。入组后接受多纳非尼(100 mg po bid)联合TACE及卡瑞利珠单抗(200 mg iv Q3W)转化治疗2个周期,不超过4个周期,经评估符合手术指征后进行手术切除。主要研究终点为主要病理缓解(major pathologic response, MPR)率,次要研究终点包括部分病理缓解(partial pathologic response, pPR)率、客观缓解率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、转化成功率、无复发生存期(relapse-free survival, RFS)、无事件生存期(event-free survival, EFS)、总生存期(overall survival, OS)以及安全性指标等。结果 受试者经三联治疗后转化成功率为70.0%,其中7例(50.0%)达到MPR,6例(42.9%)达到pPR,mRECIST标准评估ORR为75.0%,DCR为95.0%。中位EFS为9.46个月(95%CI:5.22~13.71个月),中位OS为19.48个月(95%CI:10.50~28.47个月),中位RFS为9.63个月(95%CI:5.05~14.20个月)。3级治疗相关不良事件(treatment-related adverse events, TRAE)的发生率25.0%,未发生4~5级不良事件。结论 多纳非尼联合TACE及卡瑞利珠单抗转化治疗初始不可切除的HCC疗效优异,安全性良好。Objective To observe and assess the efficacy and safety of donafenib combined with TACE and camrelizumab as conversion therapy in patients with initial unresectable HCC.Methods It was a prospective,single-arm,single center,and phaseⅡclinical study.A total of 20 initial unresectable HCC patients who had not received any systemic treatment were enrolled.The patients received donafenib(100mg po bid),TACE and camrelizumab(200mg iv Q3W)for at least 2 up to 4 cycles,followed by investigator assessment and surgical resection.The primary endpoint was the rate of MPR,and the secondary endpoints included the rate of pPR,ORR,DCR,conversion resection rate,RFS,EFS,OS and adverse events(AEs).Results 70.0%(14/20)patients were successfully converted to resectable,7(50.0%,7/14)achieved MPR,6(42.9%,6/14)achieved pPR.Based on mRECIST criteria,the ORR was 75.0%,and the DCR was 95.0%.Median EFS was 9.46 months(95%CI:5.22-13.71 months),median OS was 19.48 months(95%CI:10.50-28.47 months),median RFS was 9.63 months(95%CI:5.05-14.20 months).Grade 3 TRAEs was 25.0%,no patient experienced a Grade 4 or 5 TRAE.Conclusion These preliminary results suggested that conversion therapy with donafenib,TACE and camrelizumab was safe and effective forinitial unresectable HCC.

关 键 词：肝细胞癌 经肝动脉栓塞化疗 甲苯磺酸多纳非尼 卡瑞利珠单抗 转化治疗 

分 类 号：R735.7[医药卫生—肿瘤]