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Efficacy of Αtezolizumab–Βevacizumab in BCLC-C cirrhotic patients with hepatocellular carcinoma according to the type of disease progression, the type of BCLC-C and liver disease severity

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Abstract

Purpose

The aim of our study was to evaluate, under real-life conditions, survival of patients with advanced HCC (BCLC-C), either initially presenting in that stage or migrating from BCLC-A to BCLC-C within 2 years after curative LR/RFA, treated either with Atezolizumab–Bevacizumab or TKIs.

Methods

Sixty-four cirrhotic patients with advanced HCC, who either initially presented as BCLC-C and were treated with Atezo–Bev (group A, N = 23) or TKIs (group B, N = 15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR/RFA and were either treated with Atezo–Bev (group C, N = 12) or TKIs (group D, N = 14), were retrospectively evaluated.

Results

The four groups were comparable for all baseline parameters (demographics/platelets/liver disease etiology/diabetes/varices/Child–Pugh stage/ALBI grade) except for CPT score and MELD-Na. Using Cox-regression analysis, we observed that survival of group C after systemic treatment onset was significantly higher compared to group A (HR 3.71, 1.20–11.46, p = 0.02) and presented a trend to statistical significance when compared to group D (HR 3.14, 0.95–10.35, p = 0.06), adjusted for liver disease severity scores. When all BCLC-C patients classified as such due to PS only were excluded from the study, a trend for the same survival benefit in group C was shown, even in the most difficult-to-treat population with extrahepatic disease or macrovascular invasion.

Conclusion

Cirrhotic patients with advanced HCC initially diagnosed in BCLC-C, exhibit the worst survival irrespective of treatment schedule, whereas patients progressing to BCLC-C following disease recurrence after LR/RFA, seem to mostly benefit from Atezo–Bev, even patients with extrahepatic disease and/or macrovascular invasion. Liver disease severity seems to drive survival of these patients.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

HCC:

Hepatocellular carcinoma

BCLC:

Barcelona clinic liver cancer

LR:

Liver resection

RFA:

Radiofrequency ablation

Atezo–Bev:

Atezolizumab–Bevacizumab

TKI:

Tyrosine kinase inhibitor

CPT:

Child–Pugh score

MELD-Na:

Model for end-stage liver disease with sodium

PDL1:

Programmed-death ligand 1

VEGF:

Vascular endothelial growth factor

OS:

Overall survival

PFS:

Progression-free survival

ORR:

Objective response rates

CT:

Computed tomography

MRI:

Magnetic resonance imaging

AFP:

A-fetoprotein

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

ALD:

Alcoholic liver disease

NAFLD:

Non-alcoholic liver disease

SAAG:

Serum ascites albumin gradient

PS:

Performance status

ECOG:

Eastern Cooperative Oncology Group

NK cells:

Natural killer cells

References

  • Abou-Alfa GK, Meyer T, Cheng AL et al (2018) Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 379(1):54–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azam F, Latif MF, Farooq A et al (2019) Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) score for cancer patients by oncology healthcare professionals. Case Rep Oncol 12(3):728–736

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen HY, Lu SN, Hung CH, Wang JH, Chen CH, Yen YH, Kuo YH, Kee KM (2020) Predicting outcomes for recurrent hepatocellular carcinoma within Milan criteria after complete radiofrequency ablation. PLoS One 15(11):e0242113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng AL, Qin S, Ikeda M et al (2022) Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol 76(4):862–873

    Article  CAS  PubMed  Google Scholar 

  • Coates A, Porzsolt F, Osoba D (1997) Quality of life in oncology practice: prognostic value of EORTC QLQ-C30 scores in patients with advanced malignancy. Eur J Cancer 33(7):1025–1030

    Article  CAS  PubMed  Google Scholar 

  • De Re V, Rossetto A, Rosignoli A, Muraro E, Racanelli V, Tornesello ML, Zompicchiatti A, Uzzau A (2022) Hepatocellular carcinoma intrinsic cell death regulates immune response and prognosis. Front Oncol 12:897703. https://doi.org/10.3389/fonc.2022.897703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong SC, Bai DS, Wang FA et al (2022) Radiofrequency ablation is an inferior option to liver resection for solitary hepatocellular carcinoma ≤ 5 cm without cirrhosis: a population-based study with stratification by tumor size [published online ahead of print, 2022 Aug 8]. Hepatobiliary Pancreat Dis Int S1499-3872(22):00187-4.

  • Donne R, Lujambio A (2022) The liver cancer immune microenvironment: therapeutic implications for hepatocellular carcinoma [published online ahead of print, 2022 Aug 21]. Hepatology. https://doi.org/10.1002/hep.32740

    Article  Google Scholar 

  • Finn RS, Qin S, Ikeda M et al (2020) Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 382(20):1894–1905

    Article  CAS  PubMed  Google Scholar 

  • Foerster F, Gairing SJ, Ilyas SI, Galle PR (2022) Emerging immunotherapy for HCC: a guide for hepatologists. Hepatology 75(6):1604–1626

    Article  PubMed  Google Scholar 

  • Freitas ACT, Rampim AT, Nunes CP, Coelho JCU (2019) Impact of meld sodium on liver transplantation waiting list. Arq Bras Cir Dig 32(3):e1460. https://doi.org/10.1590/0102-672020190001e1460

    Article  PubMed  PubMed Central  Google Scholar 

  • Giraud J, Chalopin D, Blanc JF, Saleh M (2021) Hepatocellular carcinoma immune landscape and the potential of immunotherapies. Front Immunol 12:655697 (Published 2021 Mar 18)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hack SP, Spahn J, Chen M et al (2020) IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation [published correction appears in Future Oncol. 2020 Oct;16(29):2371]. Future Oncol 16(15):975–989

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa K, Kokudo N, Makuuchi M et al (2013) Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based on a Japanese nationwide survey [published correction appears in J Hepatol. 2013 Sep;59(3):641]. J Hepatol 58(4):724–729

    Article  PubMed  Google Scholar 

  • Johnson PJ, Berhane S, Kagebayashi C et al (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 33(6):550–558

    Article  PubMed  Google Scholar 

  • Kamath PS, Wiesner RH, Malinchoc M et al (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33(2):464–470

    Article  CAS  PubMed  Google Scholar 

  • Kudo M (2021) Adjuvant immunotherapy after curative treatment for hepatocellular carcinoma. Liver Cancer. 10(5):399–403 (Published 2021 Sep 6)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):52–60

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Brú C, Bruix J (1999a) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19(3):329–338

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Bustamante J, Castells A et al (1999b) Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 29(1):62–67

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390

    Article  CAS  PubMed  Google Scholar 

  • Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM (2006) Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 243(2):229–235

    Article  PubMed  PubMed Central  Google Scholar 

  • Reig M, Forner A, Rimola J et al (2022) BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 76(3):681–693

    Article  PubMed  Google Scholar 

  • Sas Z, Cendrowicz E, Weinhäuser I, Rygiel TP (2022) Tumor microenvironment of hepatocellular carcinoma: challenges and opportunities for new treatment options. Int J Mol Sci 23(7):3778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherman M (2008) Recurrence of hepatocellular carcinoma. N Engl J Med 359(19):2045–2047

    Article  CAS  PubMed  Google Scholar 

  • Simonetti RG, Cammà C, Fiorello F, Politi F, D’Amico G, Pagliaro L (1991) Hepatocellular carcinoma. A worldwide problem and the major risk factors. Dig Dis Sci 36(7):962–972

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Toom S, Avula A, Kumar V, Rahma OE (2020) The immune modulation effect of locoregional therapies and its potential synergy with immunotherapy in hepatocellular carcinoma. J Hepatocell Carcinoma 10(7):11–17

    Article  Google Scholar 

  • Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS (2017) Immuno-thermal ablations—boosting the anticancer immune response. J Immunother Cancer 5(1):78

    Article  PubMed  PubMed Central  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249

    Article  PubMed  Google Scholar 

  • Yamashita T, Kudo M, Ikeda K et al (2020) REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. J Gastroenterol 55(1):113–122

    Article  CAS  PubMed  Google Scholar 

  • Yang W, Yan K, Goldberg SN, Ahmed M, Lee JC, Wu W, Zhang ZY, Wang S, Chen MH (2016) Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment. World J Gastroenterol 22(10):2993–3005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu JH, Lee JW (2020) Limitations of the Barcelona clinic liver cancer staging treatment strategy in hepatocellular carcinoma patients with performance status 1. Ann Transl Med 8(17):1042

    Article  PubMed  PubMed Central  Google Scholar 

  • Zerbini A, Pilli M, Fagnoni F, Pelosi G, Pizzi MG, Schivazappa S, Laccabue D, Cavallo C, Schianchi C, Ferrari C, Missale G (2008) Increased immunostimulatory activity conferred to antigen-presenting cells by exposure to antigen extract from hepatocellular carcinoma after radiofrequency thermal ablation. J Immunother 31:271–282

    Article  PubMed  Google Scholar 

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Funding

No funding was received for this study.

Author information

Authors and Affiliations

  1. Academic Department of Internal Medicine-Hepatogastroenterology Unit, General and Oncology Hospital of Kifisia “Agioi Anargyroi”, National and Kapodistrian University of Athens, Timiou Stavrou and Noufaron 14, Kalyftaki, N. Kifisia, 14564, Athens, Greece

    Pantzios Spyridon, Syriha Antonia, Mandilara Dionysia, Stathopoulou Ioanna, Barla Georgia, Ptohis Nikolaos, Galanis Petros & Elefsiniotis Ioannis

Authors
  1. Pantzios Spyridon
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  2. Syriha Antonia
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  3. Mandilara Dionysia
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  4. Stathopoulou Ioanna
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  5. Barla Georgia
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  6. Ptohis Nikolaos
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  7. Galanis Petros
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  8. Elefsiniotis Ioannis
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Contributions

Conceptualization: PS, SA, EI; methodology: PS, SA, MD, EI; software: GP; validation: BG, SI, EI; formal analysis: GP; investigation: PS; resources: PS, SA, MD, SI, BG, PN; data curation: PS, GP, EI; writing—original draft preparation: PS, EI; writing—review and editing: PS, EI; visualization: PS, GP; supervision: EI; project administration: PS, SA, MD, BG, SI, PN, GP, EI; funding acquisition: none.

Corresponding author

Correspondence to Pantzios Spyridon.

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Conflict of interest

All authors of this article have no conflict of interest to declare.

Ethics approval

Written informed consent was collected from all the alive patients and the study protocol was in accordance with the Declaration of Helsinki and was evaluated and approved by the Ethics Committee/Scientific Board of the General and Oncology Hospital of Kifisia ‘‘Agioi Anargyroi”, Athens, Greece (Date 18-07-2022, No. 987).

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Written informed consent was collected from all the alive patients included in the study.

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Spyridon, P., Antonia, S., Dionysia, M. et al. Efficacy of Αtezolizumab–Βevacizumab in BCLC-C cirrhotic patients with hepatocellular carcinoma according to the type of disease progression, the type of BCLC-C and liver disease severity. J Cancer Res Clin Oncol 149, 9253–9261 (2023). https://doi.org/10.1007/s00432-023-04846-4

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