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, DH ORCID: 0000-0002-7147-5703, Ma, YT, Peck-Radosavljevic, M, Ross, P, Graham, J, Fartoux, L, Deptala, A, Studeny, M, Schnell, D, Hocke, J
et al (show 2 more authors) (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.

Access the full-text of this item by clicking on the Open Access link.

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: Article
Uncontrolled Keywords: Hepatocellular carcinoma, Phase II trials
Depositing User: Symplectic Admin
Date Deposited: 09 Jan 2019 09:44
Last Modified: 19 Jan 2023 01:07
DOI: 10.1038/s41416-018-0051-8
Open Access URL: https://www.nature.com/articles/s41416-018-0051-8
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3031032