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Role of the alpha-fetoprotein response in immune checkpoint inhibitor-based treatment of patients with hepatocellular carcinoma

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

The dynamics of serum alpha-fetoprotein (AFP) level have been found to be a useful predictor of therapeutic responsiveness in patients with hepatocellular carcinoma (HCC). We evaluated whether AFP changes were able to accurately reflect imaging-based responses and predict prognosis in patients receiving therapies including immune-checkpoint inhibitors (ICIs).

Methods

A total of 108 HCC patients with baseline serum AFP ≥ 20 ng/mL who received ICI-based treatment were included. We evaluated AFP-based responses, coupled with radiographic responses by RECIST, at 6–10 (time-point 1, TP1) and 14–18 weeks (time-point 2, TP2) of therapy in terms of the change of AFP from baseline, with a > 20% decrease or increase in level corresponding to the AFP response and progression, respectively. We examined the correlations between AFP and imaging-based responses, and the prognostic implications of the AFP-based measure.

Results

Based on AFP change, there were 24 and 20 responders and 74 and 24 progressors at TP1 and TP2, respectively. The AFP responders yielded radiological objective responses in 90.9% (10/11) and 93.8% (15/16) of the cases at TP1 and TP2, respectively, compared with only 1.4% and none, respectively, of the AFP progressors at the corresponding times. The agreement between progression by RECIST and increased AFP level at the two time-points was 93.8% and 95.0%, respectively. The accuracy of the AFP-based criterion for predicting radiologic response/progression was comparable at TP1 and TP2. Both “AFP responder” and “AFP progressor” at TP1 or TP2 independently predicted the overall survival of patients (adjusted hazard ratios [95% confidence intervals], 0.360 [0.174–0.743] and 0.315 [0.117–0.850]; and 2.525 [1.362–4.679] and 3.908 [1.563–9.769], respectively).

Conclusion

Our study suggests that on-treatment AFP changes can complement imaging findings and provide prognostic information for evaluating patients with AFP-producing HCC treated with ICI-based regimens.

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Funding

This study was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (NRF-2017R1E1A1A01074298).

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea

    Ha Il Kim

  2. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea

    Jihye Lim & Ju Hyun Shim

Authors
  1. Ha Il Kim
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  2. Jihye Lim
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Contributions

HIK and JHS contributed to the study concept and design, the acquisition, analysis and interpretation of data, statistical analysis, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. JL contributed to the acquisition of data and critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Ju Hyun Shim.

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Conflict of interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the Institutional Review Board (IRB No. 2019-1573) of the Asan Medical Center, which waived the requirement for informed consent.

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Kim, H.I., Lim, J. & Shim, J.H. Role of the alpha-fetoprotein response in immune checkpoint inhibitor-based treatment of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 148, 2069–2077 (2022). https://doi.org/10.1007/s00432-021-03727-y

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  • DOI: https://doi.org/10.1007/s00432-021-03727-y

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