Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study

References

• Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi:10.3322/caac.21492
   PubMed Web of Science ®Google Scholar
• Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J. 2021;134(7):783–791. doi:10.1097/cm9.0000000000001474
   PubMed Web of Science ®Google Scholar
• Grandhi MS, Kim AK, Ronnekleiv-Kelly SM, et al. Hepatocellular carcinoma: from diagnosis to treatment. Surg Oncol. 2016;25(2):74–85. doi:10.1016/j.suronc.2016.03.002
   PubMed Web of Science ®Google Scholar
• Xu XF, Xing H, Han J, et al. Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China. JAMA Surg. 2019;154(3):209–217. doi:10.1001/jamasurg.2018.4334
   PubMed Web of Science ®Google Scholar
• Wang H, Lu Z, Zhao X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. J Hematol Oncol. 2019;12(1):133. doi:10.1186/s13045-019-0806-6
   PubMed Web of Science ®Google Scholar
• Huang A, Yang XR, Chung WY, Dennison AR, Zhou J. Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther. 2020;5(1):146. doi:10.1038/s41392-020-00264-x
   PubMed Web of Science ®Google Scholar
• Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34. doi:10.1016/s1470-2045(08)70285-7
   PubMed Web of Science ®Google Scholar
• Kudo M, Finn RS, 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. doi:10.1016/s0140-6736(18)30207-1
   PubMed Web of Science ®Google Scholar
• Qin S, Bi F, Gu S, et al. Donafenib versus sorafenib in first-line treatment of unresectable or metastatic hepatocellular carcinoma: a randomized, open-label, parallel-controlled Phase II-III trial. J Clin Oncol. 2021;39(27):3002–3011. doi:10.1200/jco.21.00163
   PubMed Web of Science ®Google Scholar
• Liu JKH, Irvine AF, Jones RL, Samson A. Immunotherapies for hepatocellular carcinoma. Cancer Med. 2022;11(3):571–591. doi:10.1002/cam4.4468
   PubMed Web of Science ®Google Scholar
• Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, Phase 2 trial. Lancet Oncol. 2020;21(4):571–580. doi:10.1016/s1470-2045(20)30011-5
   PubMed Web of Science ®Google Scholar
• Rizzo A, Ricci AD, Gadaleta-Caldarola G, Brandi G. First-line immune checkpoint inhibitor-based combinations in unresectable hepatocellular carcinoma: current management and future challenges. Expert Rev Gastroenterol Hepatol. 2021;15(11):1245–1251. doi:10.1080/17474124.2021.1973431
   PubMed Web of Science ®Google Scholar
• Song Y, Fu Y, Xie Q, et al. Anti-angiogenic agents in combination with immune checkpoint inhibitors: a promising strategy for cancer treatment. Front Immunol. 2020;11:1956. doi:10.3389/fimmu.2020.01956
   PubMed Web of Science ®Google Scholar
• Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–1905. doi:10.1056/NEJMoa1915745
   PubMed Web of Science ®Google Scholar
• Finn RS, Ikeda M, Zhu AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol. 2020;38(26):2960–2970. doi:10.1200/jco.20.00808
   PubMed Web of Science ®Google Scholar
• Rizzo A, Ricci AD. PD-L1, TMB, and other potential predictors of response to immunotherapy for hepatocellular carcinoma: how can they assist drug clinical trials? Expert Opin Investig Drugs. 2022;31(4):415–423. doi:10.1080/13543784.2021.1972969
   PubMed Web of Science ®Google Scholar
• Han K, Kim JH. Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system. World J Gastroenterol. 2015;21(36):10327–10335. doi:10.3748/wjg.v21.i36.10327
   PubMed Web of Science ®Google Scholar
• Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline. Eur J Cancer. 2009;45(2):228–247. doi:10.1016/j.ejca.2008.10.026
   PubMed Web of Science ®Google Scholar
• Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60. doi:10.1055/s-0030-1247132
   PubMed Web of Science ®Google Scholar
• Song PF, Xu N, Li Q. Efficacy and Safety of anlotinib for elderly patients with previously treated extensive-stage SCLC and the prognostic significance of common adverse reactions. Cancer Manag Res. 2020;12:11133–11143. doi:10.2147/cmar.s275624
   PubMed Web of Science ®Google Scholar
• Galle PR, Dufour JF, Peck-Radosavljevic M, Trojan J, Vogel A. Systemic therapy of advanced hepatocellular carcinoma. Future Oncol. 2021;17(10):1237–1251. doi:10.2217/fon-2020-0758
   PubMed Web of Science ®Google Scholar
• Ikeda K, Kudo M, Kawazoe S, et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2017;52(4):512–519. doi:10.1007/s00535-016-1263-4
   PubMed Web of Science ®Google Scholar
• Yamashita T, Kudo M, Ikeda K, et al. REFLECT-A phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. J Gastroenterol. 2020;55(1):113–122. doi:10.1007/s00535-019-01642-1
   PubMed Web of Science ®Google Scholar
• Hao YY, Qiao YP, Cheng JD. Clinical activity and safety of anlotinib combined with PD-1 blockades for patients with previously treated small cell lung cancer. Int J Gen Med. 2021;14:10483–10493. doi:10.2147/ijgm.s337316
   PubMed Web of Science ®Google Scholar
• Wang DX, Yang X, Lin JZ, et al. Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: a retrospective, real-world study conducted in China. World J Gastroenterol. 2020;26(30):4465–4478. doi:10.3748/wjg.v26.i30.4465
   PubMed Web of Science ®Google Scholar
• Sun X, Zhang Q, Mei J, et al. Real-world efficiency of lenvatinib plus PD-1 blockades in advanced hepatocellular carcinoma: an exploration for expanded indications. BMC Cancer. 2022;22(1):293. doi:10.1186/s12885-022-09405-7
   PubMed Web of Science ®Google Scholar
• Chuma M, Uojima H, Hiraoka A, et al. Analysis of efficacy of lenvatinib treatment in highly advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein or tumor with more than 50% liver occupation: a multicenter analysis. Hepatol Res. 2021;51(2):201–215. doi:10.1111/hepr.13592
   PubMed Web of Science ®Google Scholar
• Huang X, Xu L, Ma T, et al. Lenvatinib plus immune checkpoint inhibitors improve survival in advanced hepatocellular carcinoma: a retrospective study. Front Oncol. 2021;11(751159). doi:10.3389/fonc.2021.751159
   Web of Science ®Google Scholar
• Lotfinejad P, Kazemi T, Mokhtarzadeh A, et al. PD-1/PD-L1 axis importance and tumor microenvironment immune cells. Life Sci. 2020;259:118297. doi:10.1016/j.lfs.2020.118297
   PubMed Web of Science ®Google Scholar
• Kimura T, Kato Y, Ozawa Y, et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model. Cancer Sci. 2018;109(12):3993–4002. doi:10.1111/cas.13806
   PubMed Web of Science ®Google Scholar
• Zhu Y, Sun P, Wang K, et al. Efficacy and safety of lenvatinib monotreatment and lenvatinib-based combination therapy for patients with unresectable hepatocellular carcinoma: a retrospective, real-world study in China. Cancer Cell Int. 2021;21(1):503. doi:10.1186/s12935-021-02200-7
   PubMed Web of Science ®Google Scholar
• Uchino K, Tateishi R, Shiina S, et al. Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer. 2011;117(19):4475–4483. doi:10.1002/cncr.25960
   PubMed Web of Science ®Google Scholar
• Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol. 2013;11(212). doi:10.1186/1477-7819-11-212
   Web of Science ®Google Scholar
• Jia L, Gao Y, He Y, Hooper JD, Yang P. HBV induced hepatocellular carcinoma and related potential immunotherapy. Pharmacol Res. 2020;159:104992. doi:10.1016/j.phrs.2020.104992
   PubMed Web of Science ®Google Scholar
• Wu JY, Yin ZY, Bai YN, et al. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a multicenter retrospective study. J Hepatocell Carcinoma. 2021;8:1233–1240. doi:10.2147/jhc.s332420
   PubMed Web of Science ®Google Scholar
• Finn RS, Ryoo BY, Merle P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol. 2020;38(3):193–202. doi:10.1200/jco.19.01307
   PubMed Web of Science ®Google Scholar
• Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):2461–2471. doi:10.1016/s0140-6736(17)31827-5
   PubMed Web of Science ®Google Scholar
• Wang F, Qin S, Sun X, et al. Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: data derived from a multicenter phase 2 trial. J Hematol Oncol. 2020;13(1):47. doi:10.1186/s13045-020-00886-2
   PubMed Web of Science ®Google Scholar