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Rationale of Immunotherapy in Hepatocellular Carcinoma and Its Potential Biomarkers
Open AccessArticle

Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma

1
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
3
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
4
Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
5
Institute of Clinical medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(1), 182; https://doi.org/10.3390/cancers12010182
Received: 9 December 2019 / Revised: 2 January 2020 / Accepted: 8 January 2020 / Published: 11 January 2020
(This article belongs to the Special Issue Immunotherapy in Hepatocellular Carcinoma)
Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child–Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259, p = 0.001). For patients with baseline AFP ≥10 ng/mL, significantly higher ORR (63.6% vs. 10.2%, p < 0.001) and disease control rate (81.8% vs. 14.3%, p < 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child–Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child–Pugh class determines survival by ICI treatment. View Full-Text
Keywords: alpha fetoprotein response; immune checkpoint inhibitor; unresectable hepatocellular carcinoma alpha fetoprotein response; immune checkpoint inhibitor; unresectable hepatocellular carcinoma
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Lee, P.-C.; Chao, Y.; Chen, M.-H.; Lan, K.-H.; Lee, C.-J.; Lee, I.-C.; Chen, S.-C.; Hou, M.-C.; Huang, Y.-H. Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma. Cancers 2020, 12, 182.

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