免疫检查点抑制剂联合抗血管生成靶向药物治疗晚期肝细胞癌20例临床观察

Clinical Observation of Immunotherapy Combined with Antiangiogenic Targeted Drugs in the Treatment of 20 Cases Advanced Hepatocellular Carcinoma

摘要: 目的：通过免疫检查点抑制剂(PD-1单抗)联合抗血管生成靶向药物阿帕替尼治疗晚期肝细胞肝癌20例，回顾性观察该方案临床疗效及安全性，证实该方案是晚期肝细胞癌临床治疗理想选择。方法：回顾性分析我科自2019年2月至2021年2月使用信迪利单抗(PD-1单抗)联合阿帕替尼治疗晚期肝细胞癌20例。20例患者均符合原发性肝癌诊断标准。特点均有乙型肝炎病史。其中16例为男性，女性4例。年龄42岁至67岁。中位年龄56岁。完善基线检查，排除禁忌。确诊后首选治疗方案为免疫联合抗血管生成靶向药物。信迪利单抗200 mg，三周方案。甲磺酸阿帕替尼250 mg/天，连续三周，停服一周。用药时间不少于12个月，PD及大于II级以上毒副作用停药。回顾性分析20例患者治疗期间及随访结果。结果：随访至2022年8月。评价目标肿瘤主要参考RECIST1.1标准。毒副作用主要依据CTC2.0版药物治疗毒作用分级标准，CSCO指南的免疫治疗毒作用分级标准。评效结果：6个月其中CR 0例，PR 16例，SD 4例。12个月CR 0例，PR 11例，SD 5例，PD 4例。18个月CR 0例，PR 4例，SD 7例，PD 5例，死亡4例。治疗过程及随访提示不良反应分析未出现II级以上毒副反应。结论：免疫联合抗血管生成靶向药物治疗为晚期肝癌主要治疗方法，免疫联合抗血管生成靶向药物治疗晚期肝细胞肝癌前景值得期待。本组观察结果同国内其他发表的类似研究结果相近。近期疗效高，安全可行的。

Abstract: Objective: To retrospectively observe the clinical efficacy and safety of immune checkpoint inhibitor (PD-1 mab) combined with anti-angiogenesis targeted drug apatinib in the treatment of 20 patients with advanced hepatocellular carcinoma (HCC), and confirm that the regimen is effective, safe and feasible, and is an ideal choice for the clinical treatment of advanced HCC. Methods: From February 2019 to February 2021, 20 patients that with advanced hepatocellular carcinoma were treated with sindilizumab (PD-1 mab) combined with apatinib in our department were retrospective analyzed. All 20 patients met the diagnostic criteria for primary liver cancer and had a history of hepatitis B. There were 16 males and 4 females and theirs age ranges from 42 to 67. The median age was 56 years old. All cases were improved baseline examination, eliminated contraindications and con-firmed diagnosis. The first choice of treatment is immunotherapy combined with antiangiogenic targeted drug. The treatment included Sindilizumab 200 mg every three weeks and Apatinib me-sylate 250 mg per day for three consecutive weeks then withdrawal for one week. The duration of medication was not less than 12 months. The drug was withdrawaled for progressive disease and toxic side effects greater than grade II. The results of 20 patients during treatment and follow-up were retrospectively analyzed. Results: The patients were followed up until August 2022. The tar-get tumor was evaluated using RECIST1.1 criteria. The grading of toxicity and side effects were mainly based on the toxicity grading standards of drug therapy (CTC2.0) and immunotherapy tox-icity grading standards of CSCO guidelines. After 6 months 0 case had complete remission, 16 cases had partial remission, 4 cases had stable disease. At 12 months, 0 case of CR, 11 cases of PR, 5 cases of SD and 4 cases of PD. At 18 months, there were 0 case had complete remission, 4 cases had partial remission, 7 cases had stable disease, 5 cases had progressed disease, 4 cases died. At present fol-low-up adverse reaction analysis did not show adverse reactions severer than grade II. Conclusion: Immunotherapy combined with anti-angiogenic targeted drugs is the main treatment for advanced hepatocellular carcinoma, and the prospect of immunotherapy combined with anti-angiogenic tar-geted drugs in the treatment of advanced hepatocellular carcinoma is worthy of expectation. The results of this study are similar to those of other similar studies published in China. It has high short-term efficacy, and it is safe and feasible.