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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.
- Source :
-
British journal of cancer [Br J Cancer] 2018 May; Vol. 118 (9), pp. 1162-1168. Date of Electronic Publication: 2018 Mar 22. - Publication Year :
- 2018
-
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).<br />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.<br />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%]).<br />Conclusions: Nintedanib may have similar efficacy to sorafenib in aHCC.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma, Hepatocellular epidemiology
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Disease Progression
Disease-Free Survival
Europe epidemiology
Female
Humans
Liver Neoplasms epidemiology
Liver Neoplasms metabolism
Liver Neoplasms pathology
Male
Maximum Tolerated Dose
Middle Aged
Treatment Outcome
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Carcinoma, Hepatocellular drug therapy
Indoles administration & dosage
Indoles adverse effects
Indoles pharmacokinetics
Liver Neoplasms drug therapy
Sorafenib administration & dosage
Sorafenib adverse effects
Sorafenib pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 118
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29563636
- Full Text :
- https://doi.org/10.1038/s41416-018-0051-8