Safety and Efficacy of Atezolizumab and Bevacizumab Combination as a First Line Treatment of Advanced Hepatocellular Carcinoma

References

• Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–1362. doi:10.1016/S0140-6736(22)01200-4
   PubMed Web of Science ®Google Scholar
• Rinella ME, Lazarus JV, Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;2023:1.
   Google Scholar
• Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–693. doi:10.1016/j.jhep.2021.11.018
   PubMed Web of Science ®Google Scholar
• Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390. doi:10.1056/NEJMoa0708857
   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
• Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. doi:10.1016/S0140-6736(16)32453-9
   PubMed Web of Science ®Google Scholar
• Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63. doi:10.1056/NEJMoa1717002
   PubMed Web of Science ®Google Scholar
• Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–296. doi:10.1016/S1470-2045(18)30937-9
   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
• 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 Hepatol. 2022;76(4):862–873. doi:10.1016/j.jhep.2021.11.030
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. Hepatobiliary cancers. Version 1; 2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed April 1, 2023.
   Google Scholar
• 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. Lancet Oncol. 2021;22(7):977–990. doi:10.1016/S1470-2045(21)00252-7
   PubMed Web of Science ®Google Scholar
• Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;2022:EVIDoa2100070.
   Google Scholar
• Qin S, Kudo M, Meyer T, et al. Final analysis of RATIONALE-301: randomized, phase III study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Ann Oncol. 2022;33(suppl_7):S808–S869.
   Web of Science ®Google Scholar
• Qin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023;2023:S0140–6736(23)00961–3.
   Google Scholar
• Yau T, Park JW, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77–90. doi:10.1016/S1470-2045(21)00604-5
   PubMed Web of Science ®Google Scholar
• Kelley RK, Rimassa L, Cheng AL, et al. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(8):995–1008. doi:10.1016/S1470-2045(22)00326-6
   PubMed Web of Science ®Google Scholar
• Finn RS, Kudo M, Merle P, et al. Primary results from the phase III LEAP-002 study: lenvatinib plus pembrolizumab versus lenvatinib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2022;33(suppl_7):S808–S869. doi:10.1016/j.annonc.2022.08.031
   Web of Science ®Google Scholar
• Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the checkmate 040 randomized clinical trial. JAMA Oncol. 2020;6(11):e204564. doi:10.1001/jamaoncol.2020.4564
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1016/S1470-2045(18)30351-6
   PubMed Web of Science ®Google Scholar
• Kudo M, Finn RS, Edeline J, et al. Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer. 2022;167:1–12. doi:10.1016/j.ejca.2022.02.009
   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
• Qin S, Chen Z, Fang W, et al. Pembrolizumab versus placebo as second-line therapy in patients from Asia with advanced hepatocellular carcinoma: a randomized, double-blind, phase III trial. J Clin Oncol. 2023;41(7):1434–1443. doi:10.1200/JCO.22.00620
   PubMed Web of Science ®Google Scholar
• Lee MS, Ryoo BY, Hsu CH, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol. 2020;21(6):808–820. doi:10.1016/S1470-2045(20)30156-X
   PubMed Web of Science ®Google Scholar
• Faivre S, Rimassa L, Finn RS. Molecular therapies for HCC: looking outside the box. J Hepatol. 2020;72(2):342–352. doi:10.1016/j.jhep.2019.09.010
   PubMed Web of Science ®Google Scholar
• Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 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
• He ARR, Numata K, Lee K-H, et al. Efficacy of atezolizumab (atezo) + bevacizumab (bev) after disease progression with atezo monotherapy in patients with previously untreated, unresectable hepatocellular carcinoma (HCC). Ann Oncol. 2020;31:S690–S690. doi:10.1016/j.annonc.2020.08.1102
   Web of Science ®Google Scholar
• Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39(suppl_3):267. doi:10.1200/JCO.2021.39.3_suppl.267
   Web of Science ®Google Scholar
• Galle PR, Finn RS, Qin S, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(7):991–1001. doi:10.1016/S1470-2045(21)00151-0
   PubMed Web of Science ®Google Scholar
• Personeni N, Rimassa L. Gauging the quality-of-life benefits of immunotherapy in hepatocellular carcinoma. Lancet Oncol. 2021;22(7):896–898. doi:10.1016/S1470-2045(21)00258-8
   PubMed Web of Science ®Google Scholar
• Li D, Toh H, Merle P, et al. Atezolizumab + bevacizumab vs sorafenib for unresectable hepatocellular carcinoma: results from older adults enrolled in IMbrave150. Ann Oncol. 2020;31:234. doi:10.1016/j.annonc.2020.04.061
   Web of Science ®Google Scholar
• Ikeda M, Zhu AX, Qin S, et al. IMbrave150: management of adverse events of special interest (AESIs) for atezolizumab (atezo) and bevacizumab (bev) in unresectable HCC. Ann Oncol. 2020;3:S629–S644.
   Google Scholar
• Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated efficacy and safety by risk status in patients (pts) receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment for unresectable hepatocellular carcinoma (HCC). Presented at AACR Virtual Annual Meeting; 2021; abs #5080.
   Google Scholar
• Breder VV, Vogel A, Merle P, et al. IMbrave150: exploratory efficacy and safety results of hepatocellular carcinoma (HCC) patients (pts) with main trunk and/or contralateral portal vein invasion (Vp4) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in a global Ph III study. J Clin Oncol. 2021;39(suppl_15):4073. doi:10.1200/JCO.21.01440
   PubMed Web of Science ®Google Scholar
• Merle P, Ducreux M, Finn RS, et al. IMbrave150: efficacy and safety of atezolizumab plus bevacizumab vs sorafenib by baseline varices status in patients with hepatocellular carcinoma. Presented at APPLE Virtual Annual Metting; 2021.
   Google Scholar
• Kudo M, Finn RS, Galle PR, et al. IMbrave150: exploratory efficacy and safety results in patients with hepatocellular carcinoma without macrovascular invasion (MVI) or extrahepatic spread (EHS) treated with atezolizumab (atezo) + bevacizumab (bev) or sorafenib (sor). Ann Oncol. 2021;32(suppl_5):S818–S818. doi:10.1016/j.annonc.2021.08.152
   Google Scholar
• Kudo M, Finn RS, Galle P, et al. IMbrave150: efficacy and safety of atezolizumab plus bevacizumab versus sorafenib in patients with Barcelona clinic liver cancer stage B Unresectable hepatocellular carcinoma: an exploratory analysis of the phase III study. Liver Cancer. 2023;12(3):238–250. doi:10.1159/000528272
   PubMed Web of Science ®Google Scholar
• Salem R, Galle P, Finn RS, et al. IMbrave150: exploratory efficacy and safety results of atezolizumab + bevacizumab vs sorafenib in patients with unresectable hepatocellular carcinoma (HCC) who had prior locoregional therapy (LRT). Presented at EASL-ILC Virtual Annual Meeting; 2021; abs #1674.
   Google Scholar
• Kudo M, Finn RS, Cheng A-L, et al. Albumin-bilirubin grade analyses of atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma: a post hoc analysis of the phase III imbrave150 study. Liver Cancer. 2023;2023:1–15.
   Google Scholar
• Shemesh CS, Chan P, Shao H, et al. Atezolizumab and bevacizumab in patients with unresectable hepatocellular carcinoma: pharmaco- kinetic and safety assessments based on hepatic impairment status and geographic region. Liver Cancer. 2021;10(5):485–499. doi:10.1159/000515817
   PubMed Web of Science ®Google Scholar
• Finn RS, Qin S, Ikeda M, et al. Complete responses (CR) in patients receiving atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in IMbrave150: a phase III clinical trial for unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2020;38(suppl_15):4596. doi:10.1200/JCO.2020.38.15_suppl.4596
   Web of Science ®Google Scholar
• Toh HC, Galle P, Zhu AX, et al. IMbrave150: exploratory efficacy and safety in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab beyond radiological progression until loss of clinical benefit in a global phase III study. J Clin Oncol. 2022;40(suppl_4):470. doi:10.1200/JCO.2022.40.4_suppl.470
   Web of Science ®Google Scholar
• Galle P, Finn RS, Cheng A-L, et al. Assessment of the impact of anti-drug antibodies on PK and clinical outcomes with atezolizumab + bevacizumab in HCC. Presented at: AACR Virtual Annual Meeting; 2021; abs #5078.
   Google Scholar
• Zhu AX, Finn RS, Ducreux M, et al. Exploratory Efficacy and safety of atezolizumab + bevacizumab vs sorafenib in patients with Hepatocellular Carcinoma (HCC) with non-viral etiology in a global phase III study. Presented at AASLD Liver Meeting; 2021; post #1060.
   Google Scholar
• Espinoza M, Muiquith M, Lim M, Zhu H, Singal AG, Hsiehchen D. Disease etiology and outcomes after atezolizumab plus bevacizumab in hepatocellular carcinoma: post-hoc analysis of imbrave150. Gastroenterology. 2023;165:286–288.e4. doi:10.1053/j.gastro.2023.02.042
   PubMed Web of Science ®Google Scholar
• Fulgenzi CAM, Murphy C, D’Alessio A, et al. IMbrave150 - Effect of early antibiotic exposure on survival of patients receiving atezolizumab plus bevacizumab but not sorafenib for unresectable HCC: a sub-analysis of the phase III IMbrave150 study. Presented at ASCO GI Annual Meeting; 2023; abs #597.
   Google Scholar
• Kudo M, Tsuchiya K, Shao -Y-Y, et al. IMbrave150: exploratory analysis to examine the association between bevacizumab (bev) ever being skipped and bev never being skipped in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bev in a global phase 3 study. Presented at ASCO GI Annual Meeting; 2023; abs #538.
   Google Scholar
• Piscaglia F, Masi G, Martinelli E, et al. Atezolizumab in combination with bevacizumab in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy: safety results from the interim analysis of the phase IIIb Italian AMETHISTA trial. Presented at EASL Liver Cancer Summit; 2023; abs #P01-01.
   Google Scholar
• Piscaglia F, Masi G, Martinelli E, et al. Efficacy of atezolizumab in combination with bevacizumab in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy: efficacy results from the interim analysis of the Phase IIIb Italian AMETHISTA trial. Presented at EASL Liver Cancer Summit; 2023; abs #P07-01.
   Google Scholar
• Fulgenzi CAM, Cheon J, D’Alessio A, et al. Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: results of the AB-real study. Eur J Cancer. 2022;175:204–213. doi:10.1016/j.ejca.2022.08.024
   PubMed Web of Science ®Google Scholar
• Aidoo-Micah G, Pinter M, Scheiner B, et al. EURopean field of practice study of atezolizumab and bevacizumab in hepatocellular carcinoma (EURAB-HCC). Presented at ILCA Annual Conference; 2022; post #93.
   Google Scholar
• Larrey E, Campion B, Evain M, et al. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC. Liver Int. 2022;42(12):2843–2854. doi:10.1111/liv.15458
   PubMed Web of Science ®Google Scholar
• Villa E, Bianchini M, Blasi A, et al. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol. 2022;76(5):1151–1184.
   PubMed Web of Science ®Google Scholar
• De Franchis R. Expanding consensus in portal hypertension: report of the baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–752. doi:10.1016/j.jhep.2015.05.022
   PubMed Web of Science ®Google Scholar
• D’Alessio A, Fulgenzi CAM, Nishida N, et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study. Hepatology. 2022;76(4):1000–1012. doi:10.1002/hep.32468
   PubMed Web of Science ®Google Scholar
• de Castro T, Jochheim LS, Bathon M, et al. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol. 2022;14:17588359221080298. doi:10.1177/17588359221080298
   Web of Science ®Google Scholar
• D’Alessio A, Fulgenzi CAM, Scheiner B, et al. The ALBI grade refines prognostic prediction in advanced hepatocellular cancer and enables risk stratification for bleeding events following atezolizumab plus bevacizumab. Presented at EASL Liver Cancer Summit; 2023; abs P03-04-YI.
   Google Scholar
• Iwamoto H, Shimose S, Noda Y, et al. Initial experience of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in real-world clinical practice. Cancers. 2021;13(11):2786. doi:10.3390/cancers13112786
   PubMed Web of Science ®Google Scholar
• Nakagawa M, Inoue M, Ogasawara S, et al. Clinical effects and emerging issues of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma from Japanese real-world practice. Cancer. 2023;129(4):590–599. doi:10.1002/cncr.34559
   PubMed Web of Science ®Google Scholar
• Cheon J, Yoo C, Hong JY, et al. Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Liver Int. 2022;42(3):674–681. doi:10.1111/liv.15102
   PubMed Web of Science ®Google Scholar
• Charonpongsuntorn C, Tanasanvimon S, Korphaisarn K, et al. Efficacy, safety, and patient-reported outcomes of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in Thailand: a multicenter prospective study. JCO Glob Oncol. 2022;8:e2200205. doi:10.1200/GO.22.00205
   PubMedGoogle Scholar
• Vithayathil M, D’Alessio A, Fulgenzi CAM, et al. Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Liver Int. 2022;42(11):2538–2547. doi:10.1111/liv.15405
   PubMed Web of Science ®Google Scholar
• Kim C, Yang H, Kim I, et al. Association of high levels of antidrug antibodies against atezolizumab with clinical outcomes and T-cell responses in patients with hepatocellular carcinoma. JAMA Oncol. 2022;8(12):1825–1829. doi:10.1001/jamaoncol.2022.4733
   PubMed Web of Science ®Google Scholar
• Zhu AX, Abbas AR, de Galarreta MR, et al. Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma. Nat Med. 2022;28(8):1599–1611. doi:10.1038/s41591-022-01868-2
   PubMed Web of Science ®Google Scholar
• Zhu AX, Dayyani F, Yen CJ, et al. Alpha-fetoprotein as a potential surrogate biomarker for atezolizumab + bevacizumab treatment of hepatocellular carcinoma. Clin Cancer Res. 2022;28(16):3537–3545. doi:10.1158/1078-0432.CCR-21-3275
   PubMed Web of Science ®Google Scholar
• Kaseb AO, Guan Y, Gok Yavuz B, et al. Serum IGF-1 scores and clinical outcomes in the phase III imbrave150 study of atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma. J Hepatocell Carcinoma. 2022;9:1065–1079. doi:10.2147/JHC.S369951
   PubMed Web of Science ®Google Scholar
• Tian Z, Hou X, Liu W, Han Z, Wei L. Macrophages and hepatocellular carcinoma. Cell Biosci. 2019;9:79. doi:10.1186/s13578-019-0342-7
   PubMed Web of Science ®Google Scholar
• Wu YL, Fulgenzi CAM, D’Alessio A, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as prognostic biomarkers in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Cancers. 2022;14(23):5834. doi:10.3390/cancers14235834
   PubMed Web of Science ®Google Scholar
• Chon H, Kim C, Yang H, et al. Correlation of high serum interleukin-6 with clinical outcome and T cell response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab. J Clin Oncol. 2023;41(suppl_4):596. doi:10.1200/JCO.2023.41.4_suppl.596
   Google Scholar
• Sonbol MB, Riaz IB, Naqvi SAA, et al. Systemic therapy and sequencing options in advanced hepatocellular carcinoma: a systematic review and network meta-analysis. JAMA Oncol. 2020;6(12):e204930. doi:10.1001/jamaoncol.2020.4930
   PubMed Web of Science ®Google Scholar
• Vogel A, Rimassa L, Sun HC, et al. Comparative efficacy of atezolizumab plus bevacizumab and other treatment options for patients with unresectable hepatocellular carcinoma: a network meta-analysis. Liver Cancer. 2021;10:240–248. doi:10.1159/000515302
   PubMed Web of Science ®Google Scholar
• Fulgenzi CAM, D’Alessio A, Airoldi C, et al. Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: a network metanalysis of phase III trials. Eur J Cancer. 2022;174:57–67. doi:10.1016/j.ejca.2022.06.058
   PubMed Web of Science ®Google Scholar
• Fong KY, Zhao JJ, Sultana R, et al. First-line systemic therapies for advanced hepatocellular carcinoma: a systematic review and patient-level network meta-analysis. Liver Cancer. 2022;12(1):7–18. doi:10.1159/000526639
   PubMed Web of Science ®Google Scholar
• Lei Q, Yan X, Zou H, et al. Efficacy and safety of monotherapy and combination therapy of immune checkpoint inhibitors as first-line treatment for unresectable hepatocellular carcinoma: a systematic review, meta-analysis and network meta-analysis. Discov Oncol. 2022;13(1):95. doi:10.1007/s12672-022-00559-1
   PubMedGoogle Scholar
• Fulgenzi CAM, Scheiner B, Korolewicz J, et al. Efficacy and safety of frontline systemic therapy for advanced HCC: a network meta-analysis of landmark phase III trials. JHEP Rep. 2023;5(5):100702. doi:10.1016/j.jhepr.2023.100702
   PubMedGoogle Scholar
• Casadei-Gardini A, Tada T, Shimose S, et al. Is atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma superior even to lenvatinib? A matching-adjusted indirect comparison. Target Oncol. 2021;16(2):249–254. doi:10.1007/s11523-021-00803-8
   PubMed Web of Science ®Google Scholar
• Jiang Y, Cai D, Shi S. Indirect comparisons via sorafenib for the comparative effectiveness of two PD-1/PD-L1 inhibitors to treat advanced hepatocellular carcinoma patients without prior systemic therapies. Clin Epidemiol. 2022;14:581–590. doi:10.2147/CLEP.S352045
   PubMed Web of Science ®Google Scholar
• Rimini M, Rimassa L, Ueshima K, et al. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis. ESMO Open. 2022;7(6):100591. doi:10.1016/j.esmoop.2022.100591
   PubMed Web of Science ®Google Scholar
• Casadei-Gardini A, Rimini M, Tada T, et al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur J Cancer. 2023;180:9–20. doi:10.1016/j.ejca.2022.11.017
   PubMed Web of Science ®Google Scholar
• Fulgenzi CAM, D’Alessio A, Scheiner B, et al. Feasibility of systemic anti-cancer therapy as an alternative to best supportive care in patients with advanced HCC and Child-Pugh B liver dysfunction. Presented at EASL Liver Cancer Summit; 2023; abs #P05-02-YI.
   Google Scholar
• Pinato DJ, Marron TU, Mishra-Kalyani PS, et al. Treatment-related toxicity and improved outcome from immunotherapy in hepatocellular cancer: evidence from an FDA pooled analysis of landmark clinical trials with validation from routine practice. Eur J Cancer. 2021;157:140–152. doi:10.1016/j.ejca.2021.08.020
   PubMed Web of Science ®Google Scholar
• Kyy N, Tan SH, Tan JJE, et al. Impact of Immune-related adverse events on efficacy of immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma. Liver Cancer. 2021;11(1):9–21. doi:10.1159/000518619
   PubMed Web of Science ®Google Scholar
• Campani C, Bamba-Funck J, Campion B, et al. Baseline ALBI score and early variation of serum AFP predict outcomes in patients with HCC treated by atezolizumab-bevacizumab. Liver Int. 2023;43(3):708–717. doi:10.1111/liv.15487
   PubMed Web of Science ®Google Scholar
• Scheiner B, Sartoris S, D’Alessio A, et al. Validation of the CRAFITY score in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab. Presented at EASL Liver Cancer Summit; 2023; abs #P01-14.
   Google Scholar
• Persano M, Rimini M, Tada T, et al. Identification of atezolizumab plus bevacizumab prognostic index via recursive partitioning analysis in HCC: the ABE index. Anticancer Res. 2023;43(4):1599–1610. doi:10.21873/anticanres.16310
   PubMed Web of Science ®Google Scholar
• Bruix J, Chan SL, Galle PR, et al. Systemic treatment of hepatocellular carcinoma: an EASL position paper. J Hepatol. 2021;75:960–974. doi:10.1016/j.jhep.2021.07.004
   PubMed Web of Science ®Google Scholar
• Rimassa L, Finn RS, Sangro B. Combination immunotherapy for hepatocellular carcinoma. J Hepatol. 2023;79:S0168–8278(23)00178–2. doi:10.1016/j.jhep.2023.03.003
   Web of Science ®Google Scholar
• Yoo C, Kim JH, Ryu MH, et al. Clinical outcomes with multikinase inhibitors after progression on first-line atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: a multinational multicenter retrospective study. Liver Cancer. 2021;10(2):107–114. doi:10.1159/000512781
   PubMed Web of Science ®Google Scholar
• Cabibbo G, Reig M, Celsa C, et al. First-line immune checkpoint inhibitor-based sequential therapies for advanced hepatocellular carcinoma: rationale for future trials. Liver Cancer. 2021;11(1):75–84. doi:10.1159/000520278
   PubMedGoogle Scholar
• Finn RS, Yau T, Hsu CH, et al. Ramucirumab for patients with advanced hepatocellular carcinoma and elevated alpha fetoprotein following non-sorafenib systemic therapy: an expansion cohort of REACH-2. Oncologist. 2022;2022:oyac183.
   Google Scholar
• Finn RS, Kudo M, Klümpen HJ, et al. Regorafenib in patients with unresectable hepatocellular carcinoma (uHCC) in routine clinical practice: exploratory analysis of overall survival (OS) in the prospective, observational REFINE study. J Clin Oncol. 2022;40(suppl_4):433. doi:10.1200/JCO.2022.40.4_suppl.433
   PubMed Web of Science ®Google Scholar
• Abou-Alfa G, Cheng A-L, Saletan S, Kelley RK, El-Khoureiry A. Clinical activity of cabozantinib in patients with advanced hepatocellular carcinoma previously treated with anti-VEGF and immuno-oncology therapy: subgroup analysis from the phase 3 CELESTIAL trial. Presented at EASL Liver Cancer Summit; 2020; #abs PB02-04.
   Google Scholar
• Chan SL, Ryoo B, Mo F, et al. A phase II clinical trial to study the efficacy of cabozantinib in patients with hepatocellular carcinoma refractory to immune checkpoint inhibitor-based treatment. Ann Oncol. 2022;33(suppl_9):S1454–S1484. doi:10.1016/j.annonc.2022.10.099
   Google Scholar
• Wong JSL, Kwok GGW, Tang V, et al. Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors. J Immunother Cancer. 2021;9(2):e001945. doi:10.1136/jitc-2020-001945
   PubMed Web of Science ®Google Scholar
• Scheiner B, Roessler D, Phen S, et al. Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma. JHEP Rep. 2022;5(1):100620. doi:10.1016/j.jhepr.2022.100620
   PubMedGoogle Scholar
• Chiou VL, Burotto M. Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 2015;33:3541–3543. doi:10.1200/JCO.2015.61.6870
   PubMed Web of Science ®Google Scholar
• Wang Q, Gao J, Wu X. Pseudoprogression and hyperprogression after checkpoint blockade. Int Immunopharmacol. 2018;58:125–135. doi:10.1016/j.intimp.2018.03.018
   PubMed Web of Science ®Google Scholar
• Cabibbo G, Aghemo A, Lai Q, et al. Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function. Dig Liver Dis. 2022;54(4):452–460. doi:10.1016/j.dld.2022.01.122
   PubMedGoogle Scholar
• Chow P, Chen M, Cheng A-L, et al. IMbrave050: phase 3 study of adjuvant atezolizumab + bevacizumab versus active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. Presented at AACR Annual Meeting; 2023; Abstract #CT003CTPL01.
   Google Scholar
• Ho WJ, Zhu Q, Durham J, et al. Neoadjuvant cabozantinib and nivolumab converts locally advanced HCC into resectable disease with enhanced antitumor immunity. Nat Cancer. 2021;2(9):891–903. doi:10.1038/s43018-021-00234-4
   PubMedGoogle Scholar
• Kaseb AO, Hasanov E, Cao HST, et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):208–218. doi:10.1016/S2468-1253(21)00427-1
   PubMed Web of Science ®Google Scholar
• D’Alessio A, Pai M, Spalding D, et al. Neoadjuvant immunotherapy with ipilimumab plus nivolumab and radiologically and pathologically quantifiable responses through modulation of the tumour microenvironment in resectable hepatocellular carcinoma. Presented at ASCO Annual Meeting; 2023; pos #4129.
   Google Scholar
• Marron TU, Fiel MI, Hamon P, et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):219–229. doi:10.1016/S2468-1253(21)00385-X
   PubMed Web of Science ®Google Scholar
• Personeni N, Rimassa L. Exploring novel avenues for neoadjuvant treatment of hepatocellular carcinoma. Lancet Gastroenterol Hepatol. 2022;7(3):198–199. doi:10.1016/S2468-1253(21)00462-3
   PubMed Web of Science ®Google Scholar
• Su D, Wu B, Shi L. Cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib as first-line treatment of unresectable hepatocellular carcinoma. JAMA Netw Open. 2021;4(2):e210037. doi:10.1001/jamanetworkopen.2021.0037
   PubMed Web of Science ®Google Scholar
• Zhang X, Wang J, Shi J, et al. Cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma. JAMA Netw Open. 2021;4(4):e214846. doi:10.1001/jamanetworkopen.2021.4846
   PubMed Web of Science ®Google Scholar
• Hou Y, Wu B. Atezolizumab plus bevacizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a cost-effectiveness analysis. Cancer Commun. 2020;40:743–745. doi:10.1002/cac2.12110
   Web of Science ®Google Scholar