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Review

Emerging immune checkpoint inhibitors for the treatment of hepatocellular carcinoma

ORCID Icon &
Pages 39-52 | Received 30 Nov 2020, Accepted 09 Mar 2021, Published online: 19 Mar 2021

References

  • Wild CP, Weiderpass E, Stewart BW, editors. World cancer report: cancer research for cancer prevention. 2020. pp. 403-412. Lyon, France:International Agency for Research on Cancer. Available from http://publications.iarc.fr/586
  • Global Burden of Disease Liver Cancer C. Akinyemiju T, Abera S, Ahmed M, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–1691.
  • Kamath PS, Kim WR. Advanced liver disease study G. the model for end-stage liver disease (MELD). Hepatology. 2007;45(3):797–805.
  • Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11(4):e1001624.
  • Lim KC, Chow PK, Allen JC, et al. Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria. Br J Surg. 2012;99(12):1622–1629.
  • Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390.
  • Finn RS, Qin S, Ikeda M, et al., Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20): 1894–1905.
  • Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342(6165):1432–1433.
  • Kienle GS. Fever in cancer treatment: coley’s therapy and epidemiologic observations. Glob Adv Health Med. 2012;1(1):92–100.
  • Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22(1):329–360.
  • Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–133.
  • Fs H, Sj O, Df M, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723.
  • Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–2028.
  • Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290.
  • Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–1813.
  • 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.
  • Kudo M, Moriguchi M, Numata K, et al. S-1 versus placebo in patients with sorafenib-refractory advanced hepatocellular carcinoma (S-CUBE): a randomised, double-blind, multicentre, phase 3 trial. Lancet Gastroenterol Hepatol. 2017;2(6):407–417.
  • Llovet JM, Decaens T, Raoul JL, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol. 2013;31(28):3509–3516.
  • Zhu AX, Kudo M, Assenat E, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. Jama. 2014;312(1):57–67.
  • 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.
  • 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.
  • 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.
  • Zhu AX, Finn RS, Galle PR, et al. Ramucirumab in advanced hepatocellular carcinoma in REACH-2: the true value of alpha-fetoprotein. Lancet Oncol. 2019;20(4):e191.
  • Finn RS, Merle P, Granito A, et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: additional analyses from the phase III RESORCE trial. J Hepatol. 2018;69(2):353–358.
  • El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–2502.
  • 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.
  • Haslam A, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Network Open. 2019;2(5):e192535.
  • Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833.
  • Georgieva M, Jp DSNL, Aguiar P Jr., et al. Cost-effectiveness of pembrolizumab as first-line therapy for advanced non-small cell lung cancer. Lung Cancer. 2018;124:248–254.
  • Hu X, Hay JW. First-line pembrolizumab in PD-L1 positive non-small-cell lung cancer: a cost-effectiveness analysis from the UK health care perspective. Lung Cancer. 2018;123:166–171.
  • Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–1127.
  • Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288–2301.
  • Burnet FM. The concept of immunological surveillance. Progress in Experimental Tumor Research. 1970;13:1–27.
  • LGd F, Carrilho FJ. Updates in immunotherapy for hepatocellular carcinoma. Hepatoma Res. 2019;5:37.
  • Wolchok JD, Saenger Y. The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation. Oncologist. 2008;13(Suppl 4):2–9.
  • Sakaguchi S, Yamaguchi T, Nomura T, et al. T cells and immune tolerance. Cell. 2008;133(5):775–787.
  • Tanaka A, Sakaguchi S. Targeting Treg cells in cancer immunotherapy. Eur J Immunol. 2019;49(8):1140–1146.
  • Tanaka A, Regulatory SS. T cells in cancer immunotherapy. Cell Res. 2017;27(1):109–118.
  • Scientific KM. Rationale for combined immunotherapy with PD-1/PD-L1 Antibodies and VEGF Inhibitors in Advanced Hepatocellular Carcinoma. Cancers (Basel). 2020;12:5.
  • Combination cancer KM. Immunotherapy with molecular targeted agents/anti-CTLA-4 antibody for hepatocellular carcinoma. Liver Cancer. 2019;8(1):1–11.
  • Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.
  • Tang J, Shalabi A, Hubbard-Lucey VM. Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol. 2018;29(1):84–91.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
  • Voron T, Marcheteau E, Pernot S, et al. Control of the immune response by pro-angiogenic factors. Front Oncol. 2014;4:70.
  • Yau TPJ, Finn RS, Cheng AL, et al. 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019;30:V874–V5.
  • Rs F, B-y R, Merle P, et al. Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2019;37(15_suppl):4004.
  • 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.
  • Qin S, Rs F, Kudo M, et al. RATIONALE 301 study: tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Future Oncol. 2019;15(16):1811–1822.
  • Hellmann MD, Rizvi NA, Goldman JW, et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017;18(1):31–41.
  • Yau T, Kang Y-K, Kim T-Y, et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): results from CheckMate 040. J clin oncol. 2019;37(15_suppl):4012.
  • Rk K, Gk A-A, Jc B, et al. Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): phase I safety and efficacy analyses. J clin oncol. 2017;35(15_suppl):4073.
  • Kelley RK, Sangro B, Harris WP, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC). J clin oncol. 2020;38:4508.
  • Gk A-A, Sl C, Furuse J, et al. A randomized, multicenter phase 3 study of durvalumab (D) and tremelimumab (T) as first-line treatment in patients with unresectable hepatocellular carcinoma (HCC): HIMALAYA study. J clin oncol. 2018;36(15_suppl): TPS4144-TPS.
  • Ax Z, Rs F, Ikeda M, et al. A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC). J clin oncol. 2020;38(15_suppl):4519.
  • Jm L, Kudo M, A-l C, et al. Lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): phase 3 LEAP-002 study. J clin oncol. 2019;37(15_suppl): TPS4152-TPS.
  • Xu J, Zhang Y, Jia R, et al. Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study. Clin Cancer Res off J Am Assoc Cancer Res. 2019;25(2):515–523.
  • Duffy AG, Ulahannan SV, Makorova-Rusher O, et al., Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2017;66(3): 545–551.
  • Kelley RK, Cheng A-L, Braiteh FS, et al. Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) versus sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy. J clin oncol. 2019;37(15_suppl): TPS4157-TPS.
  • Sangro B, Kudo M, Qin S, et al. A phase 3 study of transarterial chemoembolization combined with durvalumab followed by durvalumab ± bevacizumab in patients with locoregional HCC: EMERALD-1 2020. [cited 2021 Mar 15]. Available from: https://www.postersessiononline.eu/173580348_eu/congresos/LCS2020/aula/-P02_16_LCS2020.pdf.
  • Li L, Zhang J, Liu X, et al. Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2012;27(1):51–58.
  • Gabrielson A, Wu Y, Wang H, et al. Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC. Cancer Immunol Res. 2016;4(5):419–430.
  • Zhang X, Fu X, Li T, et al. The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: a systematic review and meta-analysis. PloS One. 2019;14(12):e0225327.
  • Zhao HQ, Li WM, Lu ZQ, et al. Roles of Tregs in development of hepatocellular carcinoma: a meta-analysis. World J Gastroenterol. 2014;20(24):7971–7978.
  • Jimenez Exposito MJ, Akce M, Montero Alvarez JL, et al. CA209-9DX: phase III, randomized, double-blind study of adjuvant nivolumab vs placebo for patients with hepatocellular carcinoma (HCC) at high risk of recurrence after curative resection or ablation. Ann Oncol. 2018;29:VIII267–VIII8.
  • Hack SP, Spahn J, Chen M, et al. IMbrave 050: a phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020;16(15):975–989.
  • Knox J, Cheng A, Cleary S, et al. A phase 3 study of durvalumab with or without bevacizumab as adjuvant therapy in patients with hepatocellular carcinoma at high risk of recurrence after curative hepatic resection or ablation: EMERALD-2. Ann Oncol. 2019;30:IV59–IV60.
  • McFarlane JJ, Kochenderfer MD, Olsen MR, et al. Safety and efficacy of nivolumab in patients with advanced clear cell renal cell carcinoma: results from the phase IIIb/IV checkmate 374 study. Clin Genitourin Cancer. 2020;18(6):469–76 e4.
  • Cohen EEW, Bell RB, Bifulco CB, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer. 2019;7(1):184.
  • Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393(10189):2404–2415.
  • Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–2121.

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