仑伐替尼联合PD-1抑制剂治疗晚期肝癌的疗效及安全性

肝脏 ›› 2022, Vol. 27 ›› Issue (8): 891-894.

仑伐替尼联合PD-1抑制剂治疗晚期肝癌的疗效及安全性

王璐, 孙小虎, 白静慧

110042 辽宁中国医科大学肿瘤医院、辽宁省肿瘤医院综合内科(王璐,白静慧),胸部放疗病区(孙小虎)

收稿日期:2022-01-29 出版日期:2022-08-31 发布日期:2022-09-30
通讯作者: 白静慧,Email:baijinghui559@163.com
基金资助:
辽宁省科学技术厅2018年省重点研发计划指导计划项目(201801788)

The therapeutic effect and adverse events of lenvatinib combined with PD-1 inhibitor in the treatment of advanced liver cancer

WANG Lu¹, SUN Xiao-hu², BAI Jing-hui¹

1. Comprehensive Internal medicine,Cancer Hospital of China Medical University,Liaoning Cancer Hospital & Institute,Shenyang 110042, China;
2. Department of Chest radiation therapy ward,Cancer Hospital of China Medical University,Liaoning Cancer Hospital & Institute,Shenyang 110042, China

Received:2022-01-29 Online:2022-08-31 Published:2022-09-30
Contact: BAI Jing-hui,Email:baijinghui559@163.com

摘要/Abstract

摘要： 目的探索仑伐替尼联合PD-1抑制剂在晚期肝癌治疗中的临床疗效及安全性。方法回顾性分析2019年1月1日—2021年1月1日于中国医科大学肿瘤医院使用仑伐替尼联合PD-1抑制剂治疗的48例晚期肝癌患者的临床资料。PD-1抑制剂选用帕博丽珠单抗。随访入组患者,使用mRECIST标准评价肝内病灶疗效,采用RECIST1.1标准评价肝外转移灶疗效。使用Kaplan-Meier法绘制生存曲线。结果 48例肝癌患者中,21例疗效评价为部分缓解,15例疗效评价为疾病稳定,12例疗效评价为疾病进展,客观缓解率为43.75％,疾病控制率为75.0％。中位无疾病进展时间 (mPFS) 为7.39个月 (95％CI: 5.88～8.92)。不良反应发生率为52.08％,最常见的不良反应为皮疹 (31.25％)、疲乏 (31.25％) 和高血压 (27.08％)。结论以仑伐替尼和PD-1抑制剂联合治疗晚期肝癌患者的临床效果显著,患者不良反应相对可控,此治疗方式是一种安全、有效的治疗方案,值得临床推广。

关键词: 肝肿瘤, 仑伐替尼, 程序性细胞死亡配体1抑制剂

Abstract: Objective To investigate the therapeutic effect and adverse events of Lenvatinib combined with PD-1 inhibitor in the treatment of advanced liver cancer.Methods A retrospective analysis was performed for the clinical data of 48 patients hospitalized with advanced liver cancer from January 1, 2019 to January 1, 2021 who were treated with Lenvatinib combined with Pabolizumab as a PD-1 inhibitor. The treatment outcome of intrahepatic lesions was evaluated with Modified Response Evaluation Criteria in Solid Tumors (mRECIST), during follow-up, and RECISTL1.1 was used to evaluate extrahepatic metastatic lesions. Kaplan-Meier method was used to evaluate the patients' survival time.Results Among the 48 patients with treatment experience, 21 achieved partial response, 15 achieved stabilization, and 12 had disease progression. The resulting Objective response rate was 43.75% and the disease control rate was 75.0%. The median time without disease progression was 7.39 (95% confidence interval 5.88-8.92) months. The incidence rate of adverse events was 52.08%. The most common adverse events were rash (31.25%), fatigue (31.25%) and hypertension (27.08%).Conclusion Lenvatinib combined with PD-1 inhibitor has a marked clinical effect in the treatment of advanced primary liver cancer, with a low incidence rate of serious adverse events It is therefore a safe and effective treatment regimen. This treatment is worthy of clinical promotion.

Key words: Liver neoplasms, Lenvatinib, PD-1 inhibitor

王璐, 孙小虎, 白静慧. 仑伐替尼联合PD-1抑制剂治疗晚期肝癌的疗效及安全性[J]. 肝脏, 2022, 27(8): 891-894.

WANG Lu, SUN Xiao-hu, BAI Jing-hui. The therapeutic effect and adverse events of lenvatinib combined with PD-1 inhibitor in the treatment of advanced liver cancer[J]. Chinese Hepatolgy, 2022, 27(8): 891-894.

参考文献

[1] Lee S, Kim S H. Reply to: "Detecting microvascular invasion in HCC with contrast enhanced MRI: Is it a good idea?". J Hepatol, 2018, 68(4): 863-864.
[2] Romero D. Combination set to transform HCC therapy. Nat Rev Clin Oncol, 2020, 17(7):389.
[3] Craig A J, von Felden J, Garcia-Lezana T, et al. Tumour evolution in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2020, 17(3): 139-152.
[4] Song Y, Pan G, Chen L, et al. Loss of ATOH8 Increases Stem Cell Features of Hepatocellular Carcinoma Cells. Gastroenterology, 2015, 149(4): 1068-1081.
[5] Cheng A L, Kang Y K, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase Ⅲ randomised, doubleblind, placebo-controlled trial. Lancet Oncol, 2009, 10(1): 25-34.
[6] Qin S, Bai Y, Lim H Y, et al. Randomized, multicenter, openlabel study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol, 2013, 31(28): 3501-3508.
[7] Kudo M, Finn R S, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126): 1163-1173.
[8] Prieto J, Melero I, Sangro B. Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2015, 12(12): 681-700.
[9] Iwai Y, Terawaki S, Ikegawa M, et al. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med, 2003, 198(1): 39-50.
[10] Gao Q, Wang X Y, Qiu S J, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res, 2009, 15(3): 971-979.
[11] Mazzolini G D, Malvicini M. Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy. Trends and perspectives. Medicina (B Aires), 2018, 78(1): 29-32.
[12] Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis, 2010, 30(1): 52-60.
[13] Tai W T, Cheng A L, Shiau C W, et al. Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma. Journal of Hepatology, 2011, 55(5): 1041-1048.
[14] Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer, 2008, 122(3): 664-671.
[15] Matsui J, Funahashi Y, Uenaka T, et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res, 2008, 14(17): 5459-5465.
[16] Okamoto K, Kodama K, Takase K, et al. Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models. Cancer Lett, 2013, 340(1): 97-103.
[17] Zhu X D, Tang Z Y, Sun H C. Targeting angiogenesis for liver cancer: Past, present, and future. Genes Dis, 2020, 7(3): 328-335.
[18] Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol, 2018, 19(7): 940-952.
[19] Fukumura D, Kloepper J, Amoozgar Z, et al. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol, 2018, 15(5): 325-340.
[20] Kato Y, Tabata K, Kimura T, et al. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. PLoS One, 2019, 14(2): e212513.

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