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The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors

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A Letter to the Editor to this article was published on 08 May 2024

Abstract

Background and aims

Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy.

Methods

A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan–Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model.

Results

In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7–16.7]. Three variables (total bilirubin ≥ 17 μmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2–3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort.

Conclusions

Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.

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Data availability

Data that support the findings of this study are available from the authors upon request.

Abbreviations

AFP:

Alpha-fetoprotein

AUC:

Area under the receiver operating characteristic curve

CI:

Confidence interval

CR:

Complete response

DCR:

Disease control rate

ECOG-PS:

Eastern Cooperative Oncology Group performance status

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

ICI:

Immune checkpoint inhibitor

MDT:

Multidisciplinary team

mRECIST:

Modified response evaluation criteria in solid tumors

ORR:

Objective response rate

OS:

Overall survival

PD:

Progressive disease

PFS:

Progression-free survival

PR:

Partial response

SD:

Stable disease

TACE:

Transarterial chemoembolization

TBil:

Total bilirubin

TRAEs:

Treatment-related adverse events

uHCC:

Unresectable hepatocellular carcinoma

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–214

    Article  PubMed  Google Scholar 

  2. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–693

    Article  PubMed  Google Scholar 

  3. Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, et al. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 edition). Liver Cancer. 2020;9(6):682–720

    Article  PubMed  PubMed Central  Google Scholar 

  4. Luo XY, Wu KM, He XX. Advances in drug development for hepatocellular carcinoma: clinical trials and potential therapeutic targets. J Exp Clin Cancer Res. 2021;40(1):172

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kudo M, Finn RS, Qin S, Han K-H, Ikeda K, Piscaglia F, 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

    Article  CAS  PubMed  Google Scholar 

  6. Xing R, Gao J, Cui Q, Wang Q. Strategies to improve the antitumor effect of immunotherapy for hepatocellular carcinoma. Front Immunol. 2021;26(12): 783236

    Article  Google Scholar 

  7. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–1905

    Article  CAS  PubMed  Google Scholar 

  8. Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol. 2020;38(26):2960–2970

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kudo M, Ikeda M, Motomura K, kusaka T, Kato N, Dutcus CE, et al. A phase Ib study of lenvatinib (LEN) plus nivolumab (NIV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): study 117. J Clin Oncol. 2020;38(4_suppl):513–513

    Article  Google Scholar 

  10. Stefanini B, Ielasi L, Chen R, Abbati C, Tonnini M, Tovoli F, et al. TKIs in combination with immunotherapy for hepatocellular carcinoma. Expert Rev Anticancer Ther. 2023;23(3):279–291

    Article  CAS  PubMed  Google Scholar 

  11. Rimassa L, Finn RS, Sangro B. Combination immunotherapy for hepatocellular carcinoma. J Hepatol. 2023. https://doi.org/10.1016/j.jhep

    Article  PubMed  Google Scholar 

  12. Chang Y, Jeong SW, Young Jang J, Jae KY. Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma. Int J Mol Sci. 2020;21(21):8165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhu HD, Li HL, Huang MS, Yang WZ, Yin GW, Zhong BY, et al. Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). Signal Transduct Target Ther. 2023;8(1):58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wu JY, Yin ZY, Bai YN, Chen YF, Zhou SQ, Wang SJ, et al. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a multicenter retrospective study. J Hepatocell Carcinoma. 2021;8:1233–1240

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lencioni R, Llovet J. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(01):052–060

    Article  CAS  Google Scholar 

  16. Sun L, Xu X, Meng F, Liu Q, Wang H, Li X, et al. Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: a review. Front Oncol. 2022;28(12): 980214

    Article  Google Scholar 

  17. Wu JY, Zhang ZB, Zhou JY, Ke JP, Bai YN, Chen YF, et al. Outcomes of salvage surgery for initially unresectable hepatocellular carcinoma converted by transcatheter arterial chemoembolization combined with lenvatinib plus anti-PD-1 antibodies: a multicenter retrospective study. Liver Cancer. 2023;12(3):229–237

    Article  CAS  PubMed  Google Scholar 

  18. Kadalayil L, Benini R, Pallan L, O’Beirne J, Marelli L, Yu D, et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol. 2013;24(10):2565–2570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wu JY, Wu JY, Li YN, Qiu FN, Zhou SQ, Yin ZY, et al. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: a multicenter retrospective study. Front Oncol. 2022;21(12): 985380

    Article  Google Scholar 

  20. Lu Y, Jin J, Du Q, Hu M, Wei Y, Wang M, et al. Multi-omics analysis of the anti-tumor synergistic mechanism and potential application of immune checkpoint blockade combined with lenvatinib. Front Cell Dev Biol. 2021;9(9): 730240

    Article  PubMed  PubMed Central  Google Scholar 

  21. Qu S, Zhang X, Wu Y, Meng Y, Wu Y, Meng Y, et al. Efficacy and safety of TACE combined with lenvatinib plus PD-1 inhibitors compared with TACE alone for unresectable hepatocellular carcinoma patients: a prospective cohort study. Front Oncol. 2022;21(12): 874473

    Article  Google Scholar 

  22. Cai M, Huang W, Huang J, Shi W, Guo Y, Liang L, et al. Transarterial chemoembolization combined with lenvatinib plus PD-1 inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study. Front Immunol. 2022;1(13): 848387

    Article  Google Scholar 

  23. D’Avola D, Granito A, Torre-Aláez MDL, Piscaglia F. The importance of liver functional reserve in the non-surgical treatment of hepatocellular carcinoma. J Hepatol. 2022;76(5):1185–1198

    Article  PubMed  Google Scholar 

  24. Granito A, Facciorusso A, Sacco R, Bartalena L, Mosconi C, Cea UV, et al. TRANS-TACE: prognostic role of the transient hypertransaminasemia after conventional chemoembolization for hepatocellular carcinoma. JPM. 2021;11(10):1041

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tovoli F, Ielasi L, Casadei-Gardini A, Granito A, Foschi FG, Rovesti G, et al. Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients. J Hepatol. 2019;71(6):1175–1183

    Article  CAS  PubMed  Google Scholar 

  26. Carr BI, Guerra V, Giannini EG, Farinati F, Ciccarese F, Rapaccini GL, et al. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype. Semin Oncol. 2014;41(2):252–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen ZH, Zhang XP, Lu YG, Li LQ, Chen MS, Wen TF, et al. Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study. Hepatol Int. 2020;14(5):754–764

    Article  PubMed  Google Scholar 

  28. Pardee AD, Shi J, Butterfield LH. Tumor-derived α-fetoprotein impairs the differentiation and T cell stimulatory activity of human dendritic cells. J Immunol. 2014;193(11):5723–5732

    Article  CAS  PubMed  Google Scholar 

  29. Welland S, Leyh C, Finkelmeier F, Jefremow A, Shmanko K, Gonzalez-Carmona MA, et al. Real-world data for lenvatinib in hepatocellular carcinoma (ELEVATOR): a retrospective multicenter study. Liver Cancer. 2022;11(3):219–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Liu J, Li Z, Zhang W, Lu H, Sun H, Wang G, et al. Comprehensive treatment of trans-arterial chemoembolization plus lenvatinib followed by camrelizumab for advanced hepatocellular carcinoma patients. Front Pharmacol. 2021;18(12): 709060

    Article  Google Scholar 

  31. Zhang Y, Miao H, Xie W, Jiang S, Song Z, Huang G, et al. The PPRD score stratifies patients with hepatocellular carcinoma and portal vein tumor thrombus treated with sorafenib plus transarterial chemoembolization. Eur Radiol. 2021;31(1):232–243

    Article  CAS  PubMed  Google Scholar 

  32. Scheiner B, Pomej K, Kirstein MM, Hucke F, Finkelmeier F, Waidmann O, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy—development and validation of the CRAFITY score. J Hepatol. 2022;76(2):353–363

    Article  CAS  PubMed  Google Scholar 

  33. Kim BK, Shim JH, Kim SU, Park JY, kim DY, Ahn SH, et al. Risk prediction for patients with hepatocellular carcinoma undergoing chemoembolization: development of a prediction model. Liver Int. 2016;36(1):92–99

    Article  CAS  PubMed  Google Scholar 

  34. Sheng R, Zeng M, Jin K, Zhang Y, Wu D, Sun H. MRI-based nomogram predicts the risk of progression of unresectable hepatocellular carcinoma after combined lenvatinib and anti-PD-1 antibody therapy. Acad Radiol. 2022;29(6):819–829

    Article  PubMed  Google Scholar 

  35. Xiaoyun Z, Zhu X, Feng X, Han W, Yan M, Xie F, et al. The safety and efficacy of lenvatinib combined with TACE and PD-1 inhibitors (Len-TAP) versus TACE alone in the conversion resection for initially unresectable hepatocellular carcinoma: interim results from a multicenter prospective cohort study. Ann Oncol. 2022;33(7):870

    Article  Google Scholar 

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Funding

This study was funded by the Natural Science Foundation of Fujian Province (Grant number: 2022J011021) and the Medical Innovation Project of Health and Family Planning Commission of Fujian Province (Grant number: 2022CXA002).

Author information

Author notes

  1. Zhen-Xin Zeng and Jia-Yi Wu equally contributed to this study as co-first authors.

Authors and Affiliations

  1. The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China

    Zhen-Xin Zeng, Jia-Yi Wu, Jun-Yi Wu, Yi-Nan Li, Yang-Kai Fu, De-Yi Liu, Han Li, Xiang-Ye Ou & Mao-Lin Yan

  2. Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China

    Jia-Yi Wu, Jun-Yi Wu & Mao-Lin Yan

  3. Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Shengli Road 59, Zhangzhou, 363000, Fujian, China

    Shao-Wu Zhuang

  4. Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

    Zhi-Bo Zhang

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Contributions

Conceptualization: Z-XZ, J-YW, S-WZ, and M-LY; Data curation: Z-XZ, J-YW, J-YW, Y-NL, Y-KF, Z-BZ, D-YL, HL, and X-YO; Investigation: Y-NL, Y-KF, D-YL, HL, and X-YO; Visualization: Z-XZ and J-YW; Writing—original draft: Z-XZ and J-YW; Writing—review and editing: S-WZ and M-LY; Project administration: J-YW and Z-BZ; Supervision: S-WZ and M-LY; Funding acquisition: M-LY. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shao-Wu Zhuang or Mao-Lin Yan.

Ethics declarations

Conflict of interest

Zhen-Xin Zeng, Jia-Yi Wu, Jun-Yi Wu, Yi-Nan Li, Yang-Kai Fu, Zhi-Bo Zhang, De-Yi Liu, Han Li, Xiang-Ye Ou, Shao-Wu Zhuang and Mao-Lin Yan have no relevant financial or non-financial interests to disclose.

Ethical approval

This study protocol was reviewed and approved by the Institutional Review Board of Fujian Provincial Hospital, approval number K2022-12-042. Informed consent was obtained from all participants or their legal guardians to participate in the study.

Consent to participate

Written informed consent was obtained from the patients for their anonymized information to be published in this article.

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This article does not contain any studies with animal subjects.

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Supplementary Information

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12072_2023_10613_MOESM1_ESM.tif

Supplementary file1 Figure S1. Patient flowchart. ECOG-PS, Eastern Cooperative Oncology Group performance status; uHCC, unresectable hepatocellular carcinoma. (TIF 1045 KB)

Supplementary file2 (DOCX 19 KB)

Supplementary file3 (DOCX 19 KB)

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Zeng, ZX., Wu, JY., Wu, JY. et al. The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors. Hepatol Int 18, 651–660 (2024). https://doi.org/10.1007/s12072-023-10613-x

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