免疫治疗新时代下肝胆恶性肿瘤治疗的机遇和挑战

黄晓勇; 施国明; 周俭

doi:10.3969/j.issn.1001-5256.2022.05.001

免疫治疗新时代下肝胆恶性肿瘤治疗的机遇和挑战

DOI: 10.3969/j.issn.1001-5256.2022.05.001

复旦大学附属中山医院肝肿瘤外科，上海 200032

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：周俭对文章思路和设计有关键贡献，并对文稿进行最后审定；黄晓勇、施国明参与了研究数据的获取、分析解释，参与起草文章。

详细信息

通信作者:
周俭，zhou.jian@zs-hospital.sh.cn

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出版历程
- 收稿日期: 2022-03-10
- 录用日期: 2022-04-10
- 出版日期: 2022-05-20

Opportunities and challenges for the treatment of malignant hepatobiliary tumors in the new era of immunotherapy

Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China

More Information

Corresponding author: ZHOU Jian, E-mail: zhou.jian@zs-hospital.sh.cn(ORCID: 0000-0002-2118-1117)

摘要

摘要: 肝胆恶性肿瘤主要包括肝细胞癌(HCC)及胆道恶性肿瘤(BTC)，是我国常见的恶性肿瘤，严重威胁我国人民的生命和健康。肝胆恶性肿瘤起病隐匿，大多数患者初诊即是晚期而失去手术机会。晚期HCC治疗主要依赖系统治疗如索拉非尼、仑伐替尼、多纳非尼以及瑞格非尼、阿帕替尼和全身化疗等治疗，但效果有限。晚期BTC则主要依赖全身化疗，效果差强人意。免疫治疗时代的到来，给晚期肝胆恶性肿瘤治疗带来新希望。阿替利珠单抗联合贝伐珠单抗、信迪利单抗联合贝伐珠单抗类似物(达攸同)相继被批准用于晚期HCC的一线治疗。以化疗为基础的联合免疫检查点抑制剂(ICI)或ICI联合靶向药物等方案在晚期BTC治疗中取得进展。这些方案显著改善患者的总体生存时，伴随明显的、甚至危及生命的不良反应，值得我们高度关注。另外，以ICI为基础的联合治疗在肝胆恶性肿瘤围手术期治疗中价值有待进一步评估。
- 癌，肝细胞 /
- 胆道肿瘤 /
- 免疫抑制剂
Abstract: Malignant hepatobiliary tumors mainly include hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) and are common malignancies in China that seriously threaten the life and health of the Chinese people. Malignant hepatobiliary tumors often have an insidious onset, and most patients have lost the opportunity for surgery due to the advanced stage at initial diagnosis. The treatment of advanced HCC mainly depends on systemic therapy such as sorafenib, lenvatinib, donafenib, regorafenib, apatinib, and systemic chemotherapy, but such treatment often has a limited effect. The treatment of advanced BTC mainly relies on systemic chemotherapy, which often has an unsatisfactory effect. The advent of the era of immunotherapy brings new hope to the treatment of advanced malignant hepatobiliary tumors. Atezolizumab combined with bevacizumab and sintilimab combined with a bevacizumab biosimilar IBI305 have been approved as the first-line treatment of advanced HCC. The treatment regimens, such as Chemotherapy-based immune checkpoint inhibitor (ICI) or ICI combined with targeted drugs, have made great progress in the treatment of advanced BTC, and although these regimens can significantly improve the overall survival of patients, they often bring obvious and even life-threatening adverse reactions, which should be taken seriously by clinicians. In addition, further studies are needed to investigate the value of ICI-based combination therapy in the perioperative treatment of malignant hepatobiliary tumors.
- Carcinoma, Hepatocellular /
- Biliary Tract Neoplasms /
- Immunosuppressive Agents

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参考文献(14)

[1]	GORDAN JD, KENNEDY EB, ABOU-ALFA GK, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO Guideline[J]. J Clin Oncol, 2020, 38(36): 4317-4345. DOI: 10.1200/JCO.20.02672.
[2]	FINN RS, QIN S, IKEDA M, et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905. DOI: 10.1056/NEJMoa1915745.
[3]	VALLE J, WASAN H, PALMER DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med, 2010, 362(14): 1273-1281. DOI: 10.1056/NEJMoa0908721.
[4]	FITENI F, NGUYEN T, VERNEREY D, et al. Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: A systematic review[J]. Cancer Med, 2014, 3(6): 1502-1511. DOI: 10.1002/cam4.299.
[5]	XIE C, MCGRATH NA, MONGE BONILLA C, et al. Systemic treatment options for advanced biliary tract carcinoma[J]. J Gastroenterol, 2020, 55(10): 944-957. DOI: 10.1007/s00535-020-01712-9.
[6]	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. DOI: 10.1016/S1470-2045(21)00252-7.
[7]	ABOU-ALFA GK, CHAN SL, FURUSE J, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC)[R]. Himalaya, 2022 ASCO GI22.
[8]	CHEN Z, LU X, KORAL K. The clinical application of camrelizumab on advanced hepatocellular carcinoma[J]. Expert Rev Gastroenterol Hepatol, 2020, 14(11): 1017-1024. DOI: 10.1080/17474124.2020.1807939.
[9]	ZHU AX, MACARULLA T, JAVLE MM, et al. Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: The Phase 3 Randomized Clinical ClarIDHy trial[J]. JAMA Oncol, 2021, 7(11): 1669-1677. DOI: 10.1001/jamaoncol.2021.3836.
[10]	ABOU-ALFA GK, SAHAI V, HOLLEBECQUE A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 study[J]. Lancet Oncol, 2020, 21(5): 671-684. DOI: 10.1016/S1470-2045(20)30109-1.
[11]	PIHA-PAUL SA, OH DY, UENO M, et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies[J]. Int J Cancer, 2020, 147(8): 2190-2198. DOI: 10.1002/ijc.33013.
[12]	KOIDO S, KAN S, YOSHIDA K, et al. Immunogenic modulation of cholangiocarcinoma cells by chemoimmunotherapy[J]. Anticancer Res, 2014, 34(11): 6353-6361. https://www.ncbi.nlm.nih.gov/pubmed/25368235
[13]	FENG K, LIU Y, ZHAO Y, et al. Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase Ⅱ study[J]. J Immunother Cancer, 2020, 8(1): e000367. DOI: 10.1136/jitc-2019-000367.
[14]	HATO T, ZHU AX, DUDA DG. Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma[J]. Immunotherapy, 2016, 8(3): 299-313. DOI: 10.2217/imt.15.126.