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The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development

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Title: The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development
Authors: Pinato, DJ
Yen, C
Bettinger, D
Ramaswami, R
Arizumi, T
Ward, C
Pirisi, M
Burlone, ME
Thimme, R
Kudo, M
Sharma, R
Item Type: Journal Article
Abstract: Background: Drug development in hepatocellular carcinoma (HCC) is limited by disease heterogeneity, with hepatic reserve being a major source of variation in survival outcomes. The albumin–bilirubin (ALBI) grade is a validated index of liver function in patients with HCC. Aim: To test the accuracy of the ALBI grade in predicting post-sorafenib overall survival (PSOS) in patients who permanently discontinued treatment. Methods: From a prospectively maintained international database of 447 consecutive referrals, we derived 386 eligible patients treated with sorafenib within Barcelona Clinic Liver Cancer C stage (62%), 75% of whom were of Child class A at initiation. Clinical variables at sorafenib discontinuation were analysed for their impact on post-sorafenib overall survival using uni- and multivariable analyses. Results: Median post-sorafenib overall survival of the 386 eligible patients was 3.4 months and median sorafenib duration was 2.9 months, with commonest causes of cessation being disease progression (68%) and toxicity (24%). At discontinuation, 92 patients (24%) progressed to terminal stage, due to worsening Child class to C in 40 (10%). Median post-sorafenib overall survival in patients eligible for second-line therapies (n = 294) was 17.5, 7.5 and 1.9 months according respectively to ALBI grade 1, 2 and 3 (P < 0.001). Conclusions: The ALBI grade at sorafenib discontinuation identifies a subset of patients with prolonged stability of hepatic reserve and superior survival. This may allow improved patient selection for second-line therapies in advanced HCC.
Issue Date: 24-Jan-2017
Date of Acceptance: 24-Nov-2016
URI: http://hdl.handle.net/10044/1/48665
DOI: https://dx.doi.org/10.1111/apt.13904
ISSN: 0269-2813
Publisher: Wiley
Start Page: 714
End Page: 722
Journal / Book Title: Alimentary Pharmacology and Therapeutics
Volume: 45
Issue: 5
Copyright Statement: © 2017 John Wiley & Sons Ltd. This is the accepted version of the following article: Pinato, D. J., Yen, C., Bettinger, D., Ramaswami, R., Arizumi, T., Ward, C., Pirisi, M., Burlone, M. E., Thimme, R., Kudo, M. and Sharma, R. (2017), The albumin–bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development. Alimentary Pharmacology and Therapeutics, 45: 714–722. doi:10.1111/apt.13904, which has been published in final form at https://dx.doi.org/10.1111/apt.13904
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Pharmacology & Pharmacy
ADVANCED HEPATOCELLULAR-CARCINOMA
TARGETED THERAPIES
LIVER-CIRRHOSIS
CHILD-PUGH
ALBI GRADE
PROGNOSIS
SURVIVAL
EFFICACY
BRIVANIB
IMPACT
1103 Clinical Sciences
1115 Pharmacology And Pharmaceutical Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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