A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

Palmer, D. H. et al. (2018) A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma. British Journal of Cancer, 118(9), pp. 1162-1168. (doi: 10.1038/s41416-018-0051-8) (PMID:29563636) (PMCID:PMC5943284)

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Abstract

Background: This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC). Methods: Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression. Time-to-progression (TTP, primary endpoint), overall survival (OS) and progression-free survival (PFS) were determined. Results: Phase-I: no DLTs observed; nintedanib MTD in both groups was 200 mg bid. Phase-II: patients (N = 93) were randomised to nintedanib (n = 62) or sorafenib (n = 31); TTP was 5.5 vs. 4.6 months (HR = 1.44 [95% CI, 0.81–2.57]), OS was 11.9 vs. 11.4 months (HR = 0.88 [95% CI, 0.52–1.47]), PFS was 5.3 vs. 3.9 months (HR = 1.35 [95% CI, 0.78–2.34]), respectively (all medians). Dose intensity and tolerability favoured nintedanib. Fewer patients on nintedanib (87.1%) vs. sorafenib (96.8%) had drug-related adverse events (AEs) or grade ≥ 3 AEs (67.7% vs. 90.3%), but more patients on nintedanib (28 [45.2%]) had AEs leading to drug discontinuation than did those on sorafenib (7 [22.6%]). Conclusions: Nintedanib may have similar efficacy to sorafenib in aHCC.

Item Type:Articles
Additional Information:This work was supported by the NIHR Liverpool Biomedical Research Unit [to D.H.P], the Liverpool Experimental Cancer Medicine Centre [to D.H.P.], the NIHR/Wellcome UCLH Clinical Research Facility [to T.M.], the NIHR UCL Hospitals Biomedical Research Centre [to T.M.] and the UCL Experimental Cancer Medicine Centre [to T.M.].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Dr Janet
Authors: Palmer, D. H., Ma, Y. T., Peck-Radosavljevic, M., Ross, P., Graham, J., Fartoux, L., Deptala, A., Studeny, M., Schnell, D., Hocke, J., Loembé, A.-B., and Meyer, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
Publisher:Nature Publishing Group
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:22 March 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in British Journal of Cancer 118(9): 1162-1168
Publisher Policy:Reproduced under a Creative Commons License

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