The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development
File(s)Post_SOR_ALBI.pdf (1.26 MB)
Accepted version
Author(s)
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.
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.
Date Issued
2017-01-24
Date Acceptance
2016-11-24
Citation
Alimentary Pharmacology and Therapeutics, 2017, 45 (5), pp.714-722
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
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000394693000013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
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