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Original Article | Open Access

Evaluating Tislelizumab, Lenvatinib, and FOLFOX4-HAIC as a Conversion Therapy for Unresectable Hepatocellular Carcinoma

Kai Tana,1, Xiaojun Hea,1, Haoran Yuanb,1, Shoujie Zhaoa, Chenyu Gongc, Yaoyao Zhaoa, Haiyan Nand, Li Zanga, Zhonghua Luoe,2( ), Xilin Dua,2( )
Department of General Surgery, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an 710038, Shanxi Province, China
Department of Infectious Disease, The 964th Hospital of the People's Liberation Army of China, Changchun 130062, Jilin Province, China
Graduate School of Xi'an Medical University, Xi'an 710021, Shanxi Province, China
Department of Radiology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an 710038, Shanxi Province, China
Department of Intervention Center, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an 710038, Shanxi Province, China

1These authors share the co-first authorship.

2These authors share the co-corresponding authorship.

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Abstract

Background and aims

Conversion therapy downstages tumors and renders patients with unresectable hepatocellular carcinoma (HCC) eligible for radical resection. This study aimed to evaluate the efficacy and safety of tislelizumab plus lenvatinib and hepatic artery infusion chemotherapy with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4-HAIC) as a first-line conversion therapy.

Methods

Clinical data from HCC patients who were treated with the triple therapy between April 2021 and April 2022 were retrospectively analyzed. The primary outcome included objective response rate (ORR), disease control rate (DCR), conversion resection rate (CRR), and treatment-related adverse events (TRAEs).

Results

A total of 18 patients completed conversion therapy assessment, which ended on March 27, 2023. The patients had a median age of 55.5 (37–72) years, and 94.4% were male. According to mRECIST, tumor shrinkage was observed in all patients, with an ORR of 94.4% (17/18), a DCR of 94.4% (17/18), and a median time to response of 1.4 (0.7–3.0) months. Successful conversion was observed in 61.1% (11/18) of patients (mRECIST). The CRR and pathological complete response were 38.9% (7/18) and 57.1% (4/7), respectively. The median progression-free survival (PFS) was 17.8 months, while median overall survival was not reached. The 6-and 9-month PFS rates were 83.3% and 66.7%, respectively. The most common TRAE (16/18 patients, 88.9%) was an increase in aspartate aminotransferase levels.

Conclusion

Tislelizumab combined with lenvatinib and FOLFOX4-HAIC achieved a high conversion rate and acceptable toxicity in patients with unresectable HCC, suggesting that this combination may represent a new conversion strategy for this population.

Keywords

Hepatocellular carcinomaLenvatinibFOLFOXHepatic artery infusion chemotherapyTislelizumab

References

[1]

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCANestimates of incidence and mortality worldwide for 36 cancers in 185 countries. CACancer J Clin 2018;68: 394–424. https://doi.org/10.3322/caac.21492.
Crossref Google Scholar
[2]

Park JW, Chen M, Colombo M, et al. Global patterns of hepatocellular carcinomamanagement from diagnosis to death: the BRIDGE Study. Liver Int 2015;35: 2155–66. https://doi.org/10.1111/liv.12818.
Crossref Google Scholar
[3]

Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment ofpatients with hepatocellular carcinoma. Gastroenterology 2016;150: 835–53.https://doi.org/10.1053/j.gastro.2015.12.041.
Crossref Google Scholar
[4]

European Association for the Study of the Liver. Electronic address E E E, Europeanassociation for the study of the L. EASL clinical practice guidelines: management of hepatocellular carcinoma [J]. J Hepatol 2018;69(1): 182–236. https://doi: 10.1016/j.jhep.2018.03.019.
Crossref Google Scholar
[5]

Sun HC, Zhou J, Wang Z, et al. Chinese expert consensus on conversion therapy forhepatocellular carcinoma (2021 edition). Hepatobiliary Surg Nutr 2022;11: 227–52.https://doi.org/10.21037/hbsn-21-328.
Crossref Google Scholar
[6]

Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment ofpatients with unresectable hepatocellular carcinoma: a randomised phase 3 noninferiority trial. Lancet 2018;391: 1163–73. https://doi.org/10.1016/S0140-6736(18)30207-1.
Crossref Google Scholar
[7]

Finn RS, Ryoo BY, Merle P, et al. Pembrolizumab as second-line therapy in patientswith advanced hepatocellular carcinoma in Keynote-240: a randomized, doubleblind, phase Ⅲ trial. J Clin Oncol 2020;38: 193–202. https://doi.org/10.1200/JCO.19.01307.
Crossref Google Scholar
[8]

Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectablehepatocellular carcinoma. N Engl J Med 2020;382: 1894–905. https://doi.org/10.1056/NEJMoa1915745.
Crossref Google Scholar
[9]

Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab inpatients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol 2020;6: e204564.https://doi.org/10.1001/jamaoncol.2020.4564.
Crossref Google Scholar
[10]

Fu Z, Li X, Zhong J, et al. Lenvatinib in combination with transarterialchemoembolization for treatment of unresectable hepatocellular carcinoma(uHCC): a retrospective controlled study. Hepatology International 2021;15: 663–75. https://doi.org/10.1007/s12072-021-10184-9.
Crossref Google Scholar
[11]

Luo L, Xiao Y, Zhu G, et al. Hepatic arterial infusion chemotherapy combined withPD-1 inhibitors and tyrosine kinase inhibitors for unresectable hepatocellularcarcinoma: a tertiary medical center experience. Front Oncol 2022;12: 1004652.https://doi.org/10.3389/fonc.2022.1004652.
Crossref Google Scholar
[12]

Mei J, Tang YH, Wei W, et al. Hepatic arterial infusion chemotherapy combinedwith PD-1 inhibitors plus lenvatinib versus PD-1 inhibitors plus lenvatinib foradvanced hepatocellular carcinoma. Front Oncol 2021;11: 618206. https://doi.org/10.3389/fonc.2021.618206.
Crossref Google Scholar
[13]

Zhang J, Zhang X, Mu H, et al. Surgical conversion for initially unresectable locallyadvanced hepatocellular carcinoma using a triple combination of angiogenesisinhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy: aretrospective study. Front Oncol 2021;11: 729764. https://doi.org/10.3389/fonc.2021.729764.
Crossref Google Scholar
[14]

Qin S, Bi F, Gu S, et al. Donafenib versus sorafenib in first-line treatment ofunresectable or metastatic hepatocellular carcinoma: a randomized, open-label, parallel-controlled phase Ⅱ-Ⅲ trial. J Clin Oncol 2021;39: 3002–11. https://doi.org/10.1200/JCO.21.00163.
Crossref Google Scholar
[15]

Yau T, Park J-W, Finn RS, et al. Nivolumab versus sorafenib in advancedhepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2022;23: 77–90. https://doi.org/10.1016/s1470-2045(21)00604-5.
Crossref Google Scholar
[16]

Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advancedhepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a nonrandomised, open-label phase 2 trial. Lancet Oncol 2018;19: 940–52. https://doi.org/10.1016/S1470-2045(18)30351-6.
Crossref Google Scholar
[17]

Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treatedadvanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21: 571–80. https://doi.org/10.1016/S1470-2045(20)30011-5.
Crossref Google Scholar
[18]

Qu WF, Ding ZB, Qu XD, et al. Conversion therapy for initially unresectablehepatocellular carcinoma using a combination of toripalimab, lenvatinib plus TACE: real-world study. BJS Open 2022;6. https://doi.org/10.1093/bjsopen/zrac114.
Crossref Google Scholar
[19]

Xin Y, Cao F, Yang H, et al. Efficacy and safety of atezolizumab plus bevacizumabcombined with hepatic arterial infusion chemotherapy for advanced hepatocellularcarcinoma [J]. Front Immunol 2022;13 (1664–3224 (Electronic)): 929141, https://doi: 10.3389/fimmu.2022.929141.
Crossref Google Scholar
[20]

Lai Z, He M, Bu X, et al. Lenvatinib, toripalimab plus hepatic arterial infusionchemotherapy in patients with high-risk advanced hepatocellular carcinoma: abiomolecular exploratory, phase Ⅱ trial. Eur J Cancer 2022;174: 68–77. https://doi.org/10.1016/j.ejca.2022.07.005.
Crossref Google Scholar
[21]

Wu JY, Yin ZY, Bai YN, et al. Lenvatinib combined with anti-PD-1 antibodies plustranscatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a multicenter retrospective study. J Hepatocell Carcinoma 2021;8: 1233–40. https://doi.org/10.2147/JHC.S332420.
Crossref Google Scholar
[22]

Chen S, Xu B, Wu Z, et al. Pembrolizumab plus lenvatinib with or without hepaticarterial infusion chemotherapy in selected populations of patients with treatmentnaive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: amulticenter retrospective study. BMC Cancer 2021;21: 1126. https://doi.org/10.1186/s12885-021-08858-6.
Crossref Google Scholar
[23]

Kuzuya T, Ishigami M, Ito T, et al. Favorable radiological antitumor response at 2weeks after starting lenvatinib for patients with advanced hepatocellularcarcinoma. Hepatol Res 2020;50: 374–81. https://doi.org/10.1111/hepr.13452.
Crossref Google Scholar
[24]

Kudo M, Ueshima K, Chan S, et al. Lenvatinib as an initial treatment in patients withintermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and childpugh A liver function: a proof-of-concept study. Cancers 2019;11. https://doi.org/10.3390/cancers11081084.
Crossref Google Scholar
[25]

Cleary JM, Tanabe KT, Lauwers GY, et al. Hepatic toxicities associated with the useof preoperative systemic therapy in patients with metastatic colorectaladenocarcinoma to the liver. Oncol 2009;14: 1095–105. https://doi.org/10.1634/theoncologist.2009-0152.
Crossref Google Scholar
[26]

Kaseb AO, Vence L, Blando J, et al. Immunologic correlates of pathologic completeresponse to preoperative immunotherapy in hepatocellular carcinoma. CancerImmunol Res 2019;7: 1390–5. https://doi.org/10.1158/2326-6066.CIR-18-0605.
Crossref Google Scholar
[27]

Versluis JM, Long GV, Blank CU. Learning from clinical trials of neoadjuvantcheckpoint blockade. Nat Med 2020;26: 475–84. https://doi.org/10.1038/s41591-020-0829-0.
Crossref Google Scholar
[28]

Shen L, Guo J, Zhang Q, et al. Tislelizumab in Chinese patients with advanced solidtumors: an open-label, non-comparative, phase 1/2 study. J Immunother Cancer2020;8. https://doi.org/10.1136/jitc-2019-000437.
Crossref Google Scholar
[29]

He MK, Le Y, Li QJ, et al. Hepatic artery infusion chemotherapy using mFOLFOXversus transarterial chemoembolization for massive unresectable hepatocellularcarcinoma: a prospective non-randomized study. Chin J Cancer 2017;36: 83.https://doi.org/10.1186/s40880-017-0251-2.
Crossref Google Scholar
[30]

Li S, Zhong C, Li Q, et al. Neoadjuvant transarterial infusion chemotherapy withFOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellularcarcinoma patients beyond Milan criteria: an interim analysis of a multi-center, phase 3, randomized, controlled clinical trial. J Clin Oncol 2021;39: 4008. https://doi.org/10.1200/JCO.2021.39.15_suppl.4008.4008.
Crossref Google Scholar
[31]

Li SH, Mei J, Cheng Y, et al. Postoperative adjuvant hepatic arterial infusionchemotherapy with FOLFOX in hepatocellular carcinoma with microvascularinvasion: a multicenter, phase Ⅲ, randomized study. J Clin Oncol 2022: JCO2201142. https://doi.org/10.1200/JCO.22.01142.
Crossref Google Scholar
[32]

Li QJ, He MK, Chen HW, et al. Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellularcarcinoma: a randomized phase Ⅲ trial. J Clin Oncol 2022;40: 150–60. https://doi.org/10.1200/JCO.21.00608.
Crossref Google Scholar
[33]

Li B, Qiu J, Zheng Y, et al. Conversion to resectability using transarterialchemoembolization combined with hepatic arterial infusion chemotherapy forinitially unresectable hepatocellular carcinoma. Annals of Surgery Open 2021;2: e057. https://doi.org/10.1097/AS9.0000000000000057.
Crossref Google Scholar
[34]
Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers andperspectives. Gut 2014 May;63(5): 844–55. https://doi:10.1136/gutjnl-2013-306627.
Crossref
[35]

Torrens L, Montironi C, Puigvehi M, et al. Immunomodulatory effects of lenvatinibplus anti-programmed cell death protein 1 in mice and rationale for patientenrichment in hepatocellular carcinoma. Hepatology 2021;74:2652–69. https://doi.org/10.1002/hep.32023.
Crossref Google Scholar
[36]

Yi C, Chen L, Lin Z, et al. Lenvatinib targets FGF receptor 4 to enhance antitumorimmune response of anti-programmed cell death-1 in HCC. Hepatology 2021;74:2544–60. https://doi.org/10.1002/hep.31921.
Crossref Google Scholar
iLIVER
Volume 2 Issue 3,
September 2023
Pages 163-169
DOI: 10.1016/j.iliver.2023.08.003
Cite this article:
Tan K, He X, Yuan H, et al. Evaluating Tislelizumab, Lenvatinib, and FOLFOX4-HAIC as a Conversion Therapy for Unresectable Hepatocellular Carcinoma. iLIVER, 2023, 2(3): 163-169. https://doi.org/10.1016/j.iliver.2023.08.003

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Received: 31 May 2023
Revised: 26 July 2023
Accepted: 07 August 2023
Published: 30 August 2023
© 2023 Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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