TY - JOUR
T1 - 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
AU - Palmer, Daniel H
AU - Ma, Yuk
AU - Peck-Radosavljevic, Markus
AU - Ross, Paul
AU - Graham, J
AU - Fartoux, L.
AU - Deptala, A.
AU - Studeny, M.
AU - Schnell, D.
AU - Hocke, J.
AU - Loembe, A.-B.
AU - Meyer, T
PY - 2018/3/22
Y1 - 2018/3/22
N2 - 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.
AB - 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.
U2 - 10.1038/s41416-018-0051-8
DO - 10.1038/s41416-018-0051-8
M3 - Article
SN - 0007-0920
VL - 118
SP - 1162
EP - 1168
JO - British Journal of Cancer
JF - British Journal of Cancer
ER -