中国临床药理学杂志2025，Vol.41Issue(12)：1651-1657,7.DOI:10.13699/j.cnki.1001-6821.2025.12.001
替雷利珠联合安罗替尼治疗Ⅲ～Ⅳ期肺腺癌患者的临床研究
Clinical trial of tirelizumab combined with anlotinib in the treatment of patients with stage Ⅲ-Ⅳ lung adenocarcinoma
摘要
Abstract
Objective To explore the effects of toripalimab injection combined with anlotinib hydrochloride capsules on the serum levels of excision repair cross-complementation group 1(ERCC1)and cytokeratin 19 fragment antigen 21-1(CYFRA21-1),and to analyze the long-term prognosis and safety of patients with stage Ⅲ-Ⅳ lung adenocarcinoma.Methods Stage Ⅲ-Ⅳ lung adenocarcinoma patients were divided into treatment and control groups according to cohort method.The treatment group received anlotinib hydrochloride capsules(12 mg,once daily for 2 weeks,followed by a 1-week break,with 3-week cycles)combined with toripalimab injection(200 mg intravenously every 3 weeks).The control group received anlotinib hydrochloride capsules alone for 3 months.Clinical efficacy,serum tumor markers[CA125,CA199,carcinoembryonic antigen(CEA),CYFRA21-1],peripheral blood ERCC1 mRNA expression,immune function[CD3+,CD4+,CD8+,CD4+/CD8+],complications,and adverse drug reactions were compared between the two groups.A 2-year follow-up was conducted to observe the survival outcomes[progression-free survival(PFS)and overall survival(OS)].Results A total of 56 patients were enrolled in the treatment group,with 2 dropouts,resulting in 54 patient included in the final statistical analysis.In the control group,55 patients were enrolled,with 3 dropouts,resulting in 52 patients included in the final statistical analysis.The objective response rate(ORR)of the treatment group was 68.52％(37 cases/54 cases),significantly higher than that of the control group at 44.23％(23 cases/52 cases),with statistically significant difference(P＜0.05).After treatment,the serum CA125 levels of the treatment and control groups were(129.70±27.18)and(171.37±28.54)U·mL-1,respectively;the CA199 levels were(33.67±5.23)and(39.18±6.17)U·mL-1,respectively;the CEA levels were(23.93±3.63)and(27.98±3.30)ng·mL-1,respectively;the CYFRA21-1 levels were(324.87±51.67)and(398.63±64.60)ng·mL-1,respectively;the relative expression levels of ERCC1 mRNA in peripheral blood were 3.35±0.74 and 3.87±0.55,respectively;the CD3+levels of T lymphocytes were(45.23±4.04)％and(39.18±5.52)％,respectively;the CD4+levels were(31.09±3.57)％and(27.42±3.56)％,respectively;theCD4+/CD8+levels were 1.12±0.17 and 0.98±0.16,respectively.The above indicators of the treatment group were statistically significantly different from those of the control group(all P＜0.05).After a 2-year follow-up,the median OS time of the treatment group was 17.5 months,and that of the control group was 15.0 months;the median PFS time of the treatment group was 11.0 months,and that of the control group was 9.5 months;the 2-year OS survival rates of the treatment and control groups were 31.48％(17 cases/54 cases)and 25.00％(13 cases/52 cases),respectively;the 2-year PFS survival rates were 16.67％(9 cases/54 cases)and 9.62％(5 cases/52 cases),respectively.The main adverse drug reactions in both the control group and the treatment group included gastrointestinal reactions,leukopenia,proteinuria,hypertension,abnormal liver function,and infections.The overall incidence of adverse drug reactions was 67.31％(35 cases/52 cases)in the control group and 68.52％(37 cases 54 cases)in the treatment group.The difference between the two groups was not statistically significant(P＞0.05).Conclusion Toripalimab injection combined with anlotinib hydrochloride capsules effectively inhibits the expression levels of tumor markers and the drug resistance gene ERCC1 in patients with stage Ⅲ-Ⅳ lung adenocarcinoma,promotes immune reconstitution,and improves clinical efficacy.关键词
盐酸安罗替尼胶囊/替雷利珠单抗注射液/肺腺癌/核苷酸切除修复交错互补基因1/细胞角蛋白19片段抗原21-1Key words
anlotinib hydrochloride capsules/tislelizumab injection/lung adenocarcinoma/nucleotide excision repair cross-complementation group 1/cytokeratin 19 fragment antigen 21-1分类
医药卫生引用本文复制引用
王欢欢,张晓航,王西勇..替雷利珠联合安罗替尼治疗Ⅲ～Ⅳ期肺腺癌患者的临床研究[J].中国临床药理学杂志,2025,41(12):1651-1657,7.基金项目
宿州市科技攻关计划基金资助项目(202019) （202019）
