PMID- 29888206
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220317
IS  - 2235-1795 (Print)
IS  - 1664-5553 (Electronic)
IS  - 1664-5553 (Linking)
VI  - 7
IP  - 2
DP  - 2018 May
TI  - A Phase I/Randomized Phase II Study to Evaluate the Safety, Pharmacokinetics, and 
      Efficacy of Nintedanib versus Sorafenib in Asian Patients with Advanced 
      Hepatocellular Carcinoma.
PG  - 165-178
LID - 10.1159/000486460 [doi]
AB  - BACKGROUND: Nintedanib is an oral, triple angiokinase inhibitor of vascular 
      endothelial growth factor/platelet-derived growth factor/fibroblast growth factor 
      receptors. This randomized, multicenter, open-label, phase I/II study evaluated 
      the safety, pharmacokinetics, maximum tolerated dose (MTD) in terms of 
      dose-limiting toxicities (DLTs), and efficacy of nintedanib versus sorafenib in 
      Asian patients with unresectable advanced hepatocellular carcinoma (HCC). 
      PATIENTS AND METHODS: For the phase I portion, patients were stratified into two 
      groups according to their alanine aminotransferase/aspartate aminotransferase 
      (ALT/AST) and Child-Pugh score at baseline. For phase I, the primary endpoint was 
      determination of the MTD in terms of DLTs. For phase II, patients with a 
      Child-Pugh score of 5-6, an Eastern Cooperative Oncology Group performance score 
      </=2, and an ALT/AST </=2x the upper limit of normal were enrolled and randomized 2: 
      1 to nintedanib 200 mg twice daily (b.i.d.) (the MTD determined in phase I) or 
      sorafenib 400 mg b.i.d. continuously in 28-day cycles until intolerable adverse 
      events (AEs) or disease progression (PD); treatment beyond PD was allowed if 
      clinical benefit was perceived. The primary endpoint for phase II was time to 
      progression (TTP) by central independent review (CIR; by Response Evaluation 
      Criteria in Solid Tumors v1.0); the secondary endpoints included overall survival 
      (OS). All analyses were exploratory. RESULTS: The MTD was 200 mg in both groups. 
      For phase II, 95 patients were randomized to nintedanib (n = 63) or sorafenib (n 
      = 32). For nintedanib and sorafenib, respectively, the median CIR TTP was 2.8 vs. 
      3.7 months (hazard ratio [HR] = 1.21, 95% confidence interval [CI] 0.73-2.01) and 
      the median OS 10.2 vs. 10.7 months (HR = 0.94, 95% CI 0.59-1.49). 
      Nintedanib-treated patients had fewer grade 3 or higher AEs (56 vs. 84%), serious 
      AEs (46 vs. 56%), and AEs leading to dose reduction (19 vs. 59%) and drug 
      discontinuation (24 vs. 34%). AEs associated more frequently with nintedanib were 
      vomiting and nausea, whereas those associated more frequently with sorafenib were 
      ALT/AST increases, diarrhea, rash, and palmar-plantar erythrodysesthesia 
      syndrome. CONCLUSIONS: Nintedanib showed numerically similar efficacy to 
      sorafenib for CIR TTP and OS in Asian patients with advanced HCC and adequate 
      liver function. AEs were generally manageable.
FAU - Yen, Chia-Jui
AU  - Yen CJ
AD  - Division of Hematology and Oncology, Department of Internal Medicine, National 
      Cheng Kung University Hospital, College of Medicine, National Cheng Kung 
      University, Tainan, Taiwan.
FAU - Kim, Tae-You
AU  - Kim TY
AD  - Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Feng, Yin-Hsun
AU  - Feng YH
AD  - Chi Mei Medical Center, Yongkang, Tainan, Taiwan.
FAU - Chao, Yee
AU  - Chao Y
AD  - Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Lin, Deng-Yn
AU  - Lin DY
AD  - Chang Gung Memorial Hospital & Chang Gung University, College of Medicine, 
      Taoyuan, Taiwan.
FAU - Ryoo, Baek-Yeol
AU  - Ryoo BY
AD  - Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Huang, Dennis Chin-Lun
AU  - Huang DC
AD  - Boehringer Ingelheim Taiwan Limited, Taipei, Taiwan.
FAU - Schnell, David
AU  - Schnell D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
FAU - Hocke, Julia
AU  - Hocke J
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
FAU - Loembe, Arsene-Bienvenu
AU  - Loembe AB
AD  - Boehringer Ingelheim B.V., Alkmaar, the Netherlands.
FAU - Cheng, Ann-Lii
AU  - Cheng AL
AD  - National Taiwan University Hospital, Taipei, Taiwan.
AD  - National Taiwan University Cancer Center, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20180315
PL  - Switzerland
TA  - Liver Cancer
JT  - Liver cancer
JID - 101597993
PMC - PMC5985414
OTO - NOTNLM
OT  - Advanced hepatocellular carcinoma
OT  - Angiokinase inhibitor
OT  - Dose-limiting toxicity
OT  - Maximum tolerated dose
OT  - Nintedanib
OT  - Sorafenib
EDAT- 2018/06/12 06:00
MHDA- 2018/06/12 06:01
PMCR- 2019/05/01
CRDT- 2018/06/12 06:00
PHST- 2017/08/09 00:00 [received]
PHST- 2017/12/20 00:00 [accepted]
PHST- 2018/06/12 06:00 [entrez]
PHST- 2018/06/12 06:00 [pubmed]
PHST- 2018/06/12 06:01 [medline]
PHST- 2019/05/01 00:00 [pmc-release]
AID - lic-0007-0165 [pii]
AID - 10.1159/000486460 [doi]
PST - ppublish
SO  - Liver Cancer. 2018 May;7(2):165-178. doi: 10.1159/000486460. Epub 2018 Mar 15.