多激酶抑制剂联合TACE或PD-1抑制剂在西藏地区CNLC ⅡB~ⅢB期肝癌中的疗效和安全性分析

The efficacy and safety analysis of a multikinase inhibitor with TACE or PD-1 inhibitor in CNLC stage ⅡB~ⅢB hepato-cell-ular carcinoma in Tibet

目的 分析多激酶抑制剂联合经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)或程序性死亡蛋白-1(programmed death protein-1,PD-1)抑制剂在西藏地区中国肝癌分期(China liver cancer staging,CNLC)ⅡB~ⅢB期肝癌患者中的疗效[中位无进展生存(median progression-free survival,mPFS)时间、中位总生存(median overall survival,mOS)时间]和安全性。方法 通过检索2018年1月至2021年12月在西藏自治区人民医院肿瘤科住院的肝癌患者,其经临床或病理诊断为原发性肝癌,符合CNLC ⅡB~ⅢB期;根据治疗方案分为多激酶抑制剂联合TACE组(61例)和多激酶抑制剂联合PD-1抑制剂组(26例);根据患者治疗前后影像学检查结果等,参考实体瘤临床疗效评价标准1.1版评价疗效;通过随访记录生存情况,绘制相关生存曲线并进行亚组分析;通过相关实验室和影像学检查并结合随访结果了解两组患者不良反应发生情况,评价两组治疗方案的安全性。结果 截至2021年12月31日,多激酶抑制剂联合TACE组与多激酶抑制剂联合PD-1抑制剂组患者的mPFS时间分别为8.1个月和17.9个月,mOS时间分别为16.1个月和未达终点,比较差异均有统计学意义(均P<0.05)。在亚组分析中,两组患者mPFS时间在男性、年龄≥60岁、既往无肝癌手术史、既往无TACE治疗史、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)体力活动状态(performance status,PS)评分 1~2分、肝功Child-Pugh分级A级、甲胎蛋白≥200 ng/ml、使用仑伐替尼亚组方面比较差异均有统计学意义(均P<0.05);在亚组分析中,两组患者mOS时间在既往无TACE治疗史、未更改治疗方案亚组方面比较差异均有统计学意义(均P<0.05)。多激酶抑制剂联合PD-1抑制剂组和多激酶抑制剂联合TACE组的疾病稳定例数、部分进展例数、疾病控制率分别为21例、5例、80.8%和24例、36例、41.0%,比较差异均具有统计学意义(均P<0.05)。多激酶抑制剂联合TACE组在谷草转氨酶水平升高、胆红素水平升高、腹痛、发热方面较多激酶抑制剂联合PD-1抑制剂组更常见(均P<0.05),而在腹胀方面较少见(P<0.05)。结论 与多激酶抑制剂联合TACE相比,多激酶抑制剂联合PD-1抑制剂具有更强的抗肿瘤疗效,治疗相关不良反应可控且耐受。

Objective To analyze the median progression-free survival (mPFS),median overall survival (mOS) time and safety of a multikinase inhibitor with transcatheter arterial chemoembolization (TACE) or programmed death protein-1 (PD-1) inhibitor in patients with Chinese liver cancer staging (CNLC) stage ⅡB~ⅢB hepatocellular carcinoma in Tibet.Method By searching the hepatocellular carcinoma patients hospitalized in the Oncology Department of the People’s Hospital of Tibet Autonomous Region from January 2018 to December 2021,they were confirmed as primary liver cancer by clinical or pathology,which were in line with CNLC stage Ⅱ B~Ⅲ B;according to the treatment plan,they were divided into multikinase inhibitor with TACE group (61 cases) and multikinase inhibitor with PD-1 inhibitor group (26 cases);according to the imaging examination (CT or MRI) before and after treatment,and then refer to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) to evaluate the curative effect;the survival were recorded through follow-up,the relevant survival curves were drawn and subgroup analysis were carried out;the toxic and side effects of the two groups were understood through relevant laboratory and imaging examinations and follow-up,and the safety of the treatment schemes of the two groups were evaluated.Result As of December 31,2021,the mPFS time of the multikinase inhibitor with TACE group and the multikinase inhibitor with PD-1 inhibitor group were 8.1 months and 17.9 months,and the mOS time were 16.1 months and not reached the finish line,with significant statistical differences (all P<0.05).In subgroup analysis,there were statistically significant differences in mPFS time between the two groups in the subgroup of patients with male,age 60 years or more,always without liver cancer surgery,always with no history,Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1~2 score,Child-Pugh grade A,α-fetoprotein≥200 ng/ml,and lenvatinib group (all P<0.05).In the subgroup analysis,there were statistically significant differences in mOS time between the two groups in the subgroup of patients with no previous TACE treatment history and no change in treatment regimen (all P<0.05).The number of stable disease cases,progressive disease cases and disease control rates in the multikinase inhibitor with PD-1 inhibitor group and the multikinase inhibitor with TACE group were 21 cases,5 cases,80.8% and 24 cases,36 cases,41.0%,respectively,the differences were statistically significant (all P<0.05).In the multikinase inhibitor with TACE group,the increase of AST,bilirubin,abdominal pain and fever were more common in the multikinase inhibitor with PD-1 inhibitor group (P<0.05),while abdominal distension was less common (P<0.05).Conclusion Compared with the group of the multikinase inhibitor with TACE group,the group of the multikinase inhibitor with PD-1 inhibitor have stronger antitumor effect.Compared with the multikinase inhibitor with TACE group,the treatment-related adverse reactions in the multikinase inhibitor with PD-1 inhibitor group are controllable and tolerable.