PMID- 30920122
OWN - NLM
STAT- MEDLINE
DCOM- 20200819
LR  - 20200819
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 12
IP  - 5
DP  - 2019 Sep
TI  - Exposure-Response Modeling and Simulation of Progression-Free Survival and 
      Adverse Events of Sorafenib Treatment in Patients With Advanced Thyroid Cancer.
PG  - 459-469
LID - 10.1111/cts.12634 [doi]
AB  - Sorafenib is an oral multikinase inhibitor approved for the treatment of 
      differentiated thyroid carcinoma (DTC), renal cell carcinoma, and hepatocellular 
      carcinoma. In the phase III DECISION trial in patients with DTC, sorafenib 
      exposure and the incidence of some adverse events (AEs) were higher than in 
      previous trials; therefore, we analyzed exposure-response relationships, 
      including progression-free survival (PFS) and selected AEs in patients with DTC. 
      A novel, stratified prediction-corrected visual predictive check (pc-VPC) was 
      developed to show robustness of the exposure-response relationships. 
      Time-to-event simulations confirmed the benefit of the recommended dosing 
      schedule of 800 mg/day: initial doses of 800 mg/day were associated with the 
      highest PFS, whereas lower doses (600 or 400 mg/day) were associated with 
      improved tolerability but reduced PFS. A simulated dose-reduction strategy of 
      800 mg/day for an initial two cycles followed by dose reductions seemed likely to 
      maintain efficacy while possibly mitigating selected AEs (e.g., diarrhea and 
      hand-foot skin reactions).
CI  - (c) 2019 Bayer AG. Clinical and Translational Science published by Wiley 
      Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Grevel, Joachim
AU  - Grevel J
AD  - BAST Inc. Ltd., Loughborough, UK.
FAU - Jentsch, Garrit
AU  - Jentsch G
AD  - BAST Inc. Ltd., Loughborough, UK.
FAU - Austin, Rupert
AU  - Austin R
AD  - BAST Inc. Ltd., Loughborough, UK.
FAU - Prins, Nicolaas H
AU  - Prins NH
AD  - qPharmetra, Nijmegen, The Netherlands.
FAU - Lettieri, John
AU  - Lettieri J
AD  - Bayer HealthCare Pharmaceuticals, Whippany, New Jersey, USA.
FAU - Mitchell, David
AU  - Mitchell D
AD  - Mitchell Pharmaceutical Consulting, Lafayette, Colorado, USA.
FAU - Huang, Funan
AU  - Huang F
AD  - Bayer HealthCare Pharmaceuticals, Whippany, New Jersey, USA.
FAU - Brose, Marcia S
AU  - Brose MS
AD  - Department of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center 
      of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Schlumberger, Martin
AU  - Schlumberger M
AD  - Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy 
      and Universite Paris Saclay, Villejuif, France.
FAU - Meinhardt, Gerold
AU  - Meinhardt G
AD  - Bayer HealthCare Pharmaceuticals, Whippany, New Jersey, USA.
FAU - Pena, Carol E A
AU  - Pena CEA
AD  - Bayer HealthCare Pharmaceuticals, Whippany, New Jersey, USA.
FAU - Ploeger, Bart A
AU  - Ploeger BA
AD  - Bayer AG, Berlin, Germany.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190412
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 9ZOQ3TZI87 (Sorafenib)
SB  - IM
MH  - Cell Differentiation
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - *Models, Biological
MH  - Neoplasm Staging
MH  - Progression-Free Survival
MH  - Sorafenib/adverse effects/pharmacokinetics/*therapeutic use
MH  - Thyroid Neoplasms/*drug therapy/*pathology
PMC - PMC6742948
COIS- J.L., F.H., G.M., C.P., and B.P. are employees of Bayer. F.H., C.P., and B.P. own 
      stock in Bayer. M.B. and M.S. were (principle) investigators of the DECISION 
      study. Both have received consultancy fees and research support from Bayer. J.G., 
      G.J., and R.A. are employed by BAST Inc. Ltd., a Contract Research Organization 
      under contract with Bayer. N.H.P. is employed by qPharmetra, LLC, a Contract 
      Research Organization under contract with Bayer. D.M. is employed by Mitchell 
      Pharmaceutical Consulting, a CRO under contract with Bayer. Employees of BAST 
      qPharmetra and Mitchell Pharmaceutical Consulting are barred from owning stock in 
      client companies.
EDAT- 2019/03/29 06:00
MHDA- 2020/08/20 06:00
PMCR- 2019/09/01
CRDT- 2019/03/29 06:00
PHST- 2018/12/10 00:00 [received]
PHST- 2019/02/02 00:00 [accepted]
PHST- 2019/03/29 06:00 [pubmed]
PHST- 2020/08/20 06:00 [medline]
PHST- 2019/03/29 06:00 [entrez]
PHST- 2019/09/01 00:00 [pmc-release]
AID - CTS12634 [pii]
AID - 10.1111/cts.12634 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2019 Sep;12(5):459-469. doi: 10.1111/cts.12634. Epub 2019 Apr 
      12.