Clinical study of Sintilimab combined targeted therapy for intermediate and advanced primary liver cancer

Abstract

Abstract: Objective To explore the clinical effect of Sintilimab combined targeted therapy on intermediate and advanced primary liver cancer (PLC). Methods 84 patients with PLC treated from September 2019 to June 2023 at funan county people's hospital and the north district were involved and divided into two groups by random number method. The control group (42 cases) was treated with Sintilimab, and the observation group (42 cases) was treated with Sintilimab combined with bevacizumab. After 3 cycles of treatment, the levels of serum markers related to angiogenesis and tumor were measured by enzyme-linked immunosorbent assay, and the levels of immune markers were measured by flow cytometry. Kapkan-Meier curve was used for the survival analysis. Results After treatment, the disease control rate (64.29% vs 92.86%) and objective response rate (42.86% vs 76.19%) in the observation group were higher than those in the control group, and the mortality rate (23.81% vs 47.62%) was lower than that in the control group (P<0.05). The levels of CEA, AFP, CA19-9 and DCP in the observation group [(16.7±3.3) ng/mL, (138.7±27.7) ng/mL, (142.7±20.3) U/mL, (30.5±4.3) mAU/mL, respectively] were significantly lower than those in the control group [(21.4±4.2) ng/mL, (176.2±35.2) ng/mL, (165.6±23.6) U/mL, (35.2±5.1) mAU/mL, respectively] (P<0.05). The levels of CD3⁺ and CD4⁺/CD8⁺ in the observation group [(72.9±4.8) %, (1.7±0.4)] were significantly higher than those in the control group [(68.4±4.5) %, (1.4±0.3)] (P<0.05). The levels of VEGF, MMP-9 and Ang-2 in the observation group were [(22.5±4.3) ng/mL, (40.5±5.2) mg/L, (21.6±3.6) μg/L, respectively] were significantly lower than those in the control group [(26.4±5.1) ng/mL, (44.6±5.5) mg/L, (25.1± 4.2) μg/L] (P<0.05). Conclusion Sintilimab combined with bevacizumab is effective in the treatment of advanced PLC. The levels of tumor markers and angiogenesis-related factors are decreased, the immune function and survival rate are improved, and the drug is safe.

Key words: Primary liver cancer, Middle and late stage, Sindilimab, Bevacizumab, Clinical effect

DONG Yan-bing, NIU Meng, LUO Yue-bin, WEN Ting-liang. Clinical study of Sintilimab combined targeted therapy for intermediate and advanced primary liver cancer[J]. Chinese Hepatolgy, 2024, 29(9): 1068-1073.

References

[1] Xian L, Zhao P, Chen X, et al. Heterogeneity, inherent and acquired drug resistance in patient-derived organoid models of primary liver cancer[J]. Cell Oncol (Dordr), 2022,45(5):1019-1036.
[2] Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022,77(6):1598-1606.
[3] Wang J, Zhang L, Su Y, et al. A Novel Fluorescent Probe Strategy Activated by β-Glucuronidase for Assisting Surgical Resection of Liver Cancer[J]. Anal Chem, 2022,94(19):7012-7020.
[4] 杜尚云,翁莉,武敏. TACE联合卡瑞利珠单抗治疗中晚期原发性肝癌患者临床疗效研究[J]. 实用肝脏病杂志, 2023,26(1):116-119.
[5] Lang M, Gan L, Ren S, et al. Lenvatinib plus sintilimab with or without transarterial chemoembolization for intermediate or advanced stage hepatocellular carcinoma: a propensity score-matching cohort study[J]. Am J Cancer Res, 2023,13(6):2540-2553.
[6] Cheng AL, Qin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma[J]. J Hepatol, 2022,76(4):862-873.
[7] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 中华肝脏病杂志, 2020,28(2):112-128.
[8] Litière S, Isaac G, De Vries EGE, et al. RECIST 1.1 for response evaluation apply not only to chemotherapy-treated patients but also to targeted cancer agents: a pooled database analysis[J]. J Clin Oncol, 2019,37(13):1102-1110.
[9] National Cancer Institute. Common terminology criteria for adverse events (CTCAE) v4.0[S]. 2009.
[10] Knapen R, Korenblik R, James S, et al. The effect of microwave and radiofrequency ablation (MWA/RFA) on liver volume in patients with primary and secondary liver tumours: a retrospective analysis[J]. Cardiovasc Intervent Radiol, 2023,46(8):991-999.
[11] 岳衍晓,宁尚昆,刘吉兵,等. 晚期原发性肝癌介入治疗与联合靶向药物治疗效果对比分析[J]. 中华肿瘤防治杂志, 2021,28(10):788-791.
[12] Xie L, Qian Z, Xu J. Clinical intervention effect of TACE combined with 3DCRT in patients with primary liver cancer[J]. Am J Transl Res, 2021,13(7):7960-7967.
[13] Xu ZJ, Wei MJ, Zhang XM, et al. Effects of microwave ablation on serum Golgi protein 73 in patients with primary liver cancer[J]. World J Gastroenterol, 2022,28(29):3971-3980.
[14] Jiao HB, Wang W, Guo MN, et al. Evaluation of high-risk factors and the diagnostic value of alpha-fetoprotein in the stratification of primary liver cancer. World J Clin Cases, 2022,10(26):9264-9275.
[15] Norman JS, Li PJ, Kotwani P, et al. AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation[J]. J Hepatol, 2023,79(6):1469-1477.
[16] Ren Z, Xu J, Bai Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study[J]. Lancet Oncol, 2021,22(7):977-990.
[17] 姚博文,向俊西,郑鑫,等. 阿替利珠单克隆抗体联合贝伐珠单克隆抗体治疗初始临界可切除中晚期肝癌的临床疗效[J]. 中华消化外科杂志, 2022,21(2):303-306.
[18] 张艳,钟珊,邓欢,等. 阿替利珠单克隆抗体联合贝伐珠单克隆抗体一线治疗晚期巨块型肝细胞癌的临床疗效[J]. 中华消化外科杂志,2022,21(S1):35-40.
[19] Luo H, Lu J, Bai Y, et al. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial[J]. JAMA, 2021,326(10):916-925.
[20] 邱云,杨玫,薛红红. TACE联合超声引导下微波消融治疗特殊部位原发性肝癌患者疗效研究[J]. 实用肝脏病杂志, 2022,25(3):419-422.
[21] Li H, Zhao B, Liu Y, et al. Angiogenesis in residual cancer and roles of HIF-1α, VEGF, and MMP-9 in the development of residual cancer after radiofrequency ablation and surgical resection in rabbits with liver cancer[J]. Folia Morphol (Warsz), 2020,79(1):71-78.
[22] Liu C, Shen Y, Tan Q. Diagnostic and prognostic values of MMP-9 expression in ovarian cancer: A study based on bioinformatics analysis and meta-analysis[J]. Int J Biol Markers, 2023,38(1):15-24.
[23] Dong XF, Zhong JT, Liu TQ, et al. Angiopoietin-2 regulates vessels encapsulated by tumor clusters positive hepatocellular carcinoma nest-type metastasis via integrin α5β1[J]. Zhonghua Yi Xue Za Zhi, 2021,101(9):654-660.
[24] Volk A, Legler K, Hamester F, et al. Ang-2 is a potential molecular marker for lymphatic metastasis and better response to bevacizumab therapy in ovarian cancer[J]. J Cancer Res Clin Oncol, 2023,149(17):15957-15967.
[25] Abdel Ghafar MT, Elkhouly RA, Elnaggar MH, et al. Utility of serum neuropilin-1 and angiopoietin-2 as markers of hepatocellular carcinoma[J]. J Investig Med, 2021,69(6):1222-1229.
[26] Tewari KS, Burger RA, Enserro D, et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer[J]. J Clin Oncol, 2019,37(26):2317-2328.
[27] 郑迎春,李真,王悦,等. 贝伐珠单抗联合热灌注化疗治疗晚期卵巢癌的临床效果及对TGF-β1、 VEGF和MIF水平的影响[J]. 中国肿瘤临床与康复,2020,27(2):168-171.
[28] 高金平,朴瑛,陈娟,等. PD-1/PD-L1抑制剂联合贝伐珠单抗治疗不可切除肝癌的疗效和安全性分析[J]. 实用药物与临床,2023,26(4):300-306.
[29] 朱永东,舒桂君,王永,等. 贝伐珠单抗联合TC化疗方案治疗老年卵巢癌的疗效[J]. 中国老年学杂志,2022,42(18):4429-4432.
[30] 裴士杰,邵强,叶永青,等. 贝伐珠单抗联合白蛋白紫杉醇和卡铂治疗晚期非小细胞肺癌患者的临床研究[J]. 中国临床药理学杂志,2023,39(23):3375-3378.