Efficacy and safety of pembrolizumab in the treatment of advanced hepatocellular carcinoma: a systematic review and meta-analysis

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229–263

PubMed  Google Scholar 

Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS (2021) Hepatocellular carcinoma. Nat Rev Dis Prim 7(1):6

PubMed  Google Scholar 

Tao ZW, Cheng BQ, Zhou T, Gao YJ (2022) Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: a narrative review. Hepatobiliary Pancreat Dis Int 21(2):134–144

CAS  PubMed  Google Scholar 

Rizzo A, Ricci AD, Brandi G (2022) Trans-arterial chemoembolization plus systemic treatments for hepatocellular carcinoma: an update. J Pers Med 12(11):1788

PubMed  PubMed Central  Google Scholar 

Gordan JD, Kennedy EB, Abou-Alfa GK, Beal E, Finn RS, Gade TP, Goff L, Gupta S, Guy J, Hoang HT et al (2024) Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update. J Clin Oncol 42(15):1830–1850

CAS  PubMed  Google Scholar 

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391(10126):1163–1173

CAS  PubMed  Google Scholar 

FDA approves lenvatinib for unresectable hepatocellular carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lenvatinib-unresectable-hepatocellular-carcinoma. Accessed 18 Mar 2025

Regorafenib. https://www.fda.gov/drugs/resources-information-approved-drugs/regorafenib. Accessed 18 Mar 2025

FDA D.I.S.C.O.: FDA approval of cabozantinib for hepatocellular carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-fda-approval-cabozantinib-hepatocellular-carcinoma. Accessed 18 Mar 2025

Rizzo A, Ricci AD (2022) Challenges and future trends of hepatocellular carcinoma immunotherapy. Int J Mol Sci 23(19):11363

PubMed  PubMed Central  Google Scholar 

El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling THR et al (2017) Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 389(10088):2492–2502

CAS  PubMed  PubMed Central  Google Scholar 

Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A et al (2018) Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol 19(7):940–952

PubMed  Google Scholar 

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905

CAS  PubMed  Google Scholar 

FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-plus-bevacizumab-unresectable-hepatocellular-carcinoma. Accessed 18 Mar 2025

Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, Sukeepaisarnjaroen W, Kang YK, Van Dao T, De Toni EN et al (2022) Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid 1(8):EVIDoa2100070

FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma. Accessed 18 Mar 2025

Rizzo A, Mollica V, Marchetti A, Nuvola G, Rosellini M, Tassinari E, Molina-Cerrillo J, Myint ZW, Buchler T, Monteiro FSM et al (2022) Adjuvant PD-1 and PD-L1 inhibitors and relapse-free survival in cancer patients: the MOUSEION-04 study. Cancers (Basel) 14(17):4142

CAS  PubMed  Google Scholar 

Kwok G, Yau TC, Chiu JW, Tse E, Kwong YL (2016) Pembrolizumab (keytruda). Hum Vaccin Immunother 12(11):2777–2789

PubMed  PubMed Central  Google Scholar 

Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G, Jr., Psyrri A, Brana I, Basté N, Neupane P, et al (2023) Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study. J Clin Oncol 41(4):790–802

CAS  PubMed  Google Scholar 

Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J et al (2020) Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial. JAMA Oncol 6(10):1571–1580

PubMed  Google Scholar 

Robert C, Carlino MS, McNeil C, Ribas A, Grob JJ, Schachter J, Nyakas M, Kee D, Petrella TM, Blaustein A et al (2023) Seven-year follow-up of the phase III KEYNOTE-006 study: pembrolizumab versus ipilimumab in advanced melanoma. J Clin Oncol 41(24):3998–4003

CAS  PubMed  Google Scholar 

Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N et al (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382(9):810–821

CAS  PubMed  Google Scholar 

Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC et al (2020) Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol 38(21):2369–2379

CAS  PubMed  PubMed Central  Google Scholar 

Qin S, Chen Z, Fang W, Ren Z, Xu R, Ryoo BY, Meng Z, Bai Y, Chen X, Liu X et al (2023) 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 41(7):1434–1443

CAS  PubMed  Google Scholar 

Kuo HY, Han MZ, Liao CH, Lin YJ, Wang CT, Chen SH, Chang TT, Chen PJ, Lin SH, Chen CY et al (2022) Real-world comparative effectiveness of nivolumab versus pembrolizumab in patients with unresectable hepatocellular carcinoma. Pharmaceutics 14(11):2263

CAS  PubMed  PubMed Central  Google Scholar 

Chen YH, Tsai CH, Chen YY, Wang CC, Wang JH, Hung CH, Kuo YH (2023) Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma. BMC Cancer 23(1):810

CAS  PubMed  PubMed Central  Google Scholar 

Huang X, Xu L, Ma T, Yin X, Huang Z, Ran Y, Ni Y, Bi X, Che X (2021) Lenvatinib plus immune checkpoint inhibitors improve survival in advanced hepatocellular carcinoma: a retrospective study. Front Oncol 11:751159

CAS  PubMed  PubMed Central  Google Scholar 

Scheiner B, Kirstein MM, Hucke F, Finkelmeier F, Schulze K, von Felden J, Koch S, Schwabl P, Hinrichs JB, Waneck F et al (2019) Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort. Aliment Pharmacol Ther 49(10):1323–1333

CAS  PubMed  PubMed Central  Google Scholar 

Guven DC, Erul E, Kaygusuz Y, Akagunduz B, Kilickap S, De Luca R, Rizzo A (2023) Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data. Support Care Cancer 31(12):624

PubMed  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

PubMed  PubMed Central  Google Scholar 

Hsu YC, Lin PT, Teng W, Hsieh YC, Chen WT, Su CW, Wang CT, Chai PM, Lin CC, Lin CY et al (2024) (2024) Comparing lenvatinib/pembrolizumab with atezolizumab/bevacizumab in unresectable hepatocellular carcinoma: a real-world experience with propensity score matching analysis. Cancers (Basel) 16(20):3458

CAS  PubMed  Google Scholar 

Yarchoan M, Gane EJ, Marron TU, Perales-Linares R, Yan J, Cooch N, Shu DH, Fertig EJ, Kagohara LT, Bartha G et al (2024) Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial. Nat Med 30(4):1044–1053

CAS  PubMed  PubMed Central  Google Scholar 

Merle P, Kudo M, Edeline J, Bouattour M, Cheng AL, Chan SL, Yau T, Garrido M, Knox J, Daniele B et al (2023) Pembrolizumab as second-line therapy for advanced hepatocellular carcinoma: longer term follow-up from the phase 3 KEYNOTE-240 trial. Liver Cancer 12(4):309–320

CAS  PubMed  PubMed Central  Google Scholar 

Kudo M, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer DH, Verslype C, Zagonel V, Fartoux L, Vogel A et al (2022) 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 (Oxford, England : 1990) 167:1–12

Hong JY, Cho HJ, Sa JK, Liu X, Ha SY, Lee T, Kim H, Kang W, Sinn DH, Gwak GY et al (2022) Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial. Genome Med 14(1):1

CAS  PubMed  PubMed Central  Google Scholar 

Mahn R, Vogt A, Kupczyk P, Sadeghlar F, van Beekum K, Hüneburg R, Meyer C, Toma M, Ahmadzadehfar H, Essler M et al (2020) Programmed cell death protein 1 (PD-1)-inhibition in hepatocellular carcinoma (HCC): a single center experience. Scand J Gastroenterol 55(9):1057–1062

CAS  PubMed  Google Scholar 

Wu CJ, Lee PC, Hung YW, Lee CJ, Chi CT, Lee IC, Hou MC, Huang YH (2022) Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. Cancer immunology, immunotherapy : CII 71(11):2631–2643

CAS  PubMed  PubMed Central  Google Scholar 

Tümen D, Heumann P, Gülow K, Demirci CN, Cosma LS, Müller M, Kandulski A (2022) Pathogenesis and current treatment strategies of hepatocellular carcinoma. Biomedicines 10(12):3202

PubMed 

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