PMID- 29563636
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20220321
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 118
IP  - 9
DP  - 2018 May
TI  - 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.
PG  - 1162-1168
LID - 10.1038/s41416-018-0051-8 [doi]
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.
FAU - Palmer, D H
AU  - Palmer DH
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      Liverpool, United Kingdom. Daniel.Palmer@liverpool.ac.uk.
AD  - Clatterbridge Cancer Centre, Bebington, United Kingdom. 
      Daniel.Palmer@liverpool.ac.uk.
FAU - Ma, Y T
AU  - Ma YT
AD  - School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
FAU - Peck-Radosavljevic, M
AU  - Peck-Radosavljevic M
AD  - Department of Gastroenterology & Hepatology, Medizinische Universitat Wien, 
      Vienna, Austria.
FAU - Ross, P
AU  - Ross P
AD  - King's College Hospital NHS Foundation Trust, London, United Kingdom.
FAU - Graham, J
AU  - Graham J
AD  - Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow, United 
      Kingdom.
FAU - Fartoux, L
AU  - Fartoux L
AD  - Hopital Saint-Antoine, Paris, France.
FAU - Deptala, A
AU  - Deptala A
AD  - Central Clinical Hospital of the Ministry of Interior, Department of Oncology and 
      Hematology, Medical University of Warsaw, Warsaw, Poland.
FAU - Studeny, M
AU  - Studeny M
AD  - Boehringer Ingelheim, Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Schnell, D
AU  - Schnell D
AD  - Boehringer Ingelheim, Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Hocke, J
AU  - Hocke J
AD  - Boehringer Ingelheim, Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Loembe, A-B
AU  - Loembe AB
AD  - Boehringer Ingelheim B.V., Alkmaar, The Netherlands.
FAU - Meyer, T
AU  - Meyer T
AD  - UCL Cancer Institute, University College London, London, United Kingdom.
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180322
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Indoles)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - G6HRD2P839 (nintedanib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Hepatocellular/*drug therapy/epidemiology/metabolism/pathology
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Europe/epidemiology
MH  - Female
MH  - Humans
MH  - *Indoles/administration & dosage/adverse effects/pharmacokinetics
MH  - Liver Neoplasms/*drug therapy/epidemiology/metabolism/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - *Sorafenib/administration & dosage/adverse effects/pharmacokinetics
MH  - Treatment Outcome
PMC - PMC5943284
COIS- D.H.P reports travel expenses from Boehringer Ingelheim and grants from Bayer, 
      outside the submitted work. A-B.L., J.H., M.S., and D.S. are employees of 
      Boehringer Ingelheim. Y.T.M reports personal fees from Bayer during the conduct 
      of the study. T.M. reports consulting and conference travel expenses. M.P-R 
      reports per patient fees for a phase III trial from Boehringer Ingelheim during 
      the conduct of the study; and grants and personal fees from Bayer Healthcare, 
      Lilly, Arqle-Daiichi, and other from ONXEO, outside the submitted work. P.R., 
      J.G., L.F. and A.D report no relevant conflicts of interest.
EDAT- 2018/03/23 06:00
MHDA- 2019/06/14 06:00
PMCR- 2018/03/22
CRDT- 2018/03/23 06:00
PHST- 2017/07/27 00:00 [received]
PHST- 2018/02/12 00:00 [accepted]
PHST- 2018/01/31 00:00 [revised]
PHST- 2018/03/23 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/03/23 06:00 [entrez]
PHST- 2018/03/22 00:00 [pmc-release]
AID - 10.1038/s41416-018-0051-8 [pii]
AID - 51 [pii]
AID - 10.1038/s41416-018-0051-8 [doi]
PST - ppublish
SO  - Br J Cancer. 2018 May;118(9):1162-1168. doi: 10.1038/s41416-018-0051-8. Epub 2018 
      Mar 22.