Efficacy and safety of immune checkpoint therapy in hepatocellular carcinoma: meta-analysis

Weina Tang , Long-Teng Ma , Yang Deng , Wei Wang , Hong-Wei Zhang

Hepatoma Research ›› 2019, Vol. 5 : 19

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Hepatoma Research ›› 2019, Vol. 5:19 DOI: 10.20517/2394-5079.2019.07
Meta-Analysis
Meta-Analysis

Efficacy and safety of immune checkpoint therapy in hepatocellular carcinoma: meta-analysis

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Abstract

Aim: Immune checkpoint inhibitors (ICIs) are proven to be an effective way to treat the disease of hematologic malignancies. But there is still plenty of uncertainty about the effectiveness of ICIs on hepatocellular carcinoma. The Meta-analysis was conducted to evaluate the efficacy and safety of ICIs treatment in patients with HCC.

Methods: Four electronic databases, including PubMed, Embase, Cochrane database, and ClinicalTrials.gov, were systematically retrieved for relevant observational studies published before November 1, 2018. The objective response rate (ORR) and adverse events were analyzed. Meta and Metafor Packages in R were utilized to accomplish meta proportion analysis.

Results: A total of 462 patients from 7 studies were included in this meta-analysis. The pooled estimated ORR of ICIs was 19.8% (95% CI 16.4% to 23.7%). No substantial heterogeneity was observed among studies (Q = 2.0427, P = 0.92, I2 = 0.0%). The common adverse events on any grade were saw in increased AST (22.7%, 95%CI 13.8% to 35.2%), fatigue (20.9%, 95%CI 10.9% to 36.3%), rash (18.5%, 95%CI 8.9% to 34.4%) and pruritus (17.3%, 95%CI 13.5% to 21.8%). Increased AST (9.9%, 95%CI 4.4% to 21.0%) and increased ALT (5.8%, 95%CI 3.7% to 8.9%) were the most common adverse events on grade greater than 3.

Conclusion: Although ICIs treatment has a certain efficacy on liver cancer, it also causes some adverse events which should be noticed by clinicians.

Keywords

Hepatocellular / immune-checkpoint inhibitor / CLAT-4 / PD1/PD-L1

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Weina Tang, Long-Teng Ma, Yang Deng, Wei Wang, Hong-Wei Zhang. Efficacy and safety of immune checkpoint therapy in hepatocellular carcinoma: meta-analysis. Hepatoma Research, 2019, 5: 19 DOI:10.20517/2394-5079.2019.07

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References

[1]

Bray F,Soerjomataram I,Torre LA.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries..CA Cancer J Clin2018;68:394-424

[2]

Llovet JM,Pikarsky E,Schwartz M.Hepatocellular carcinoma..Nat Rev Dis Primers2016;2:16018

[3]

Forner A,Bruix J.Hepatocellular carcinoma..Lancet2012;379:1245-55

[4]

Giannini EG,Ciccarese F,Rapaccini GL.Prognosis of untreated hepatocellular carcinoma..Hepatology2015;61:184-90

[5]

Cheng AL,Chen Z,Qin S.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 Oncol2009;10:25-34

[6]

Llovet JM,Mazzaferro V,Gane E.Sorafenib in advanced hepatocellular carcinoma..N Engl J Med2008;359:378-90

[7]

Zitvogel L,Kroemer G.Cancer despite immunosurveillance: immunoselection and immunosubversion..Nat Rev Immunol2006;6:715-27

[8]

Chew V,Pan L,Li J.Delineation of an immunosuppressive gradient in hepatocellular carcinoma using high-dimensional proteomic and transcriptomic analyses..Proc Natl Acad Sci USA.2017;114:E5900-E09 PMCID:PMC5530700

[9]

Conway JR,Mo SS,Van Allen E.Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine..Genome Med2018;10:93 PMCID:PMC6264032

[10]

Ruggeri RM,Giuffrida G,Giovanella L.Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know)..J Endocrinol Invest2018;

[11]

Wolchok JD,Gonzalez R,Grob JJ.Overall survival with combined nivolumab and ipilimumab in advanced melanoma..N Engl J Med2017;377:1345-56 PMCID:PMC5706778

[12]

Horn L,Vokes EE,Ready N.Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057)..J Clin Oncol2017;35:3924-33 PMCID:PMC6075826

[13]

Motzer RJ,McDermott DF,Melichar B.Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma..N Engl J Med2018;378:1277-90 PMCID:PMC5972549

[14]

Moher D,Tetzlaff J,Group P.Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement..Ann Intern Med2009;151:264-9W64

[15]

Sangro B,de la Mata M,Garralda E.A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C..J Hepatol2013;59:81-8

[16]

Duffy AG,Makorova-Rusher O,Wedemeyer H.Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma..J Hepatol2017;66:545-51 PMCID:PMC5316490

[17]

Zhu AX,Edeline J,Ogasawara S.Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial..Lancet Oncol2018;19:940-52

[18]

El-Khoueiry AB,Yau T,Kudo M.Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial..Lancet2017;389:2492-502

[19]

Feng D,Shi-Chun L,Li C.Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma..Oncotarget2017;8:96649-55 PMCID:PMC5722511

[20]

Wainberg ZA,Jaeger D,Marshall J.Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC)..Journal of Clinical Oncology2017;35:4071

[21]

Kelley RK,Bendell JC,Borad MJ.Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): phase I safety and efficacy analyses..Journal of Clinical Oncology2017;35:4073

[22]

Ribas A.Cancer immunotherapy using checkpoint blockade..Science2018;359:1350-5

[23]

Clark DP.Biomarkers for immune checkpoint inhibitors: the importance of tumor topography and the challenges to cytopathology..Cancer Cytopathol2018;126:11-9

[24]

Oxnard GR,Gonen M,Hirsch BR.Response rate as a regulatory end point in single-arm studies of advanced solid tumors..JAMA Oncol2016;2:772-9 PMCID:PMC5574183

[25]

Xu F,Zhu Y.Immune checkpoint therapy in liver cancer..J Exp Clin Cancer Res2018;37:110 PMCID:PMC5975687

[26]

Planchard D,McCleod MJ,Kim YC.A phase III study of durvalumab (MEDI4736) with or without tremelimumab for previously treated patients with advanced NSCLC: rationale and protocol design of the ARCTIC study..Clin Lung Cancer2016;17:232-6.e1

[27]

Gettinger SN,Gandhi L,Antonia SJ.Overall survival and long-term safety of nivolumab (Anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer..J Clin Oncol2015;33:2004-12 PMCID:PMC4672027

[28]

Weber JS,Minor D,Gutzmer R.Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial..Lancet Oncol2015;16:375-84

[29]

Hamid O,Daud A,Hwu WJ.Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma..N Engl J Med2013;369:134-44 PMCID:PMC4126516

[30]

Powles T,Fine GD,Loriot Y.MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer..Nature.2014;515:558-62

[31]

Ansell SM,Borrello I,Scott EC.PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma..N Engl J Med2015;372:311-9 PMCID:PMC4348009

[32]

Armand P,Weller EA,Avigan DE.Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial..J Clin Oncol2013;31:4199-206 PMCID:PMC4878008

[33]

Weber JS,Hauschild A.Management of immune-related adverse events and kinetics of response with ipilimumab..J Clin Oncol2012;30:2691-7

[34]

Callahan MK.At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy..J Leukoc Biol2013;94:41-53 PMCID:PMC4051187

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