PMID- 30196106
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20190520
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 103
DP  - 2018 Nov
TI  - An extended phase Ib study of epertinib, an orally active reversible dual 
      EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours.
PG  - 17-23
LID - S0959-8049(18)31115-8 [pii]
LID - 10.1016/j.ejca.2018.07.134 [doi]
AB  - BACKGROUND: Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 
      inhibitor, has established a recommended daily dose of 800 mg in patients with 
      solid tumours. In this study, we have recruited a larger number of patients to 
      assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour 
      activity. PATIENTS AND METHODS: Patients with solid tumours expressing EGFR or 
      HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7 
      days, followed by continuous once-daily dosing from Day 8. RESULTS: We treated 76 
      patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck 
      (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade 
      I and II adverse events (AEs). The most frequent AE was diarrhoea, which was 
      generally manageable with loperamide. The objective response rate (ORR) in 
      patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs) 
      and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive 
      tumours; the ORR for HER2-positive breast and upper GI cancer populations was 
      19.0% and 20.0%. Partial response in the brain disease of one breast cancer 
      patient lasted 7.5 months. CONCLUSION: Once-daily dosing of epertinib at 800 mg 
      was well-tolerated and demonstrated promising antitumour activity in patients 
      with heavily pretreated HER2-positive breast and upper GI cancer, including those 
      with brain metastases. EUDRACT NUMBER: 2009-017817-31.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Arkenau, H-T
AU  - Arkenau HT
AD  - Sarah Cannon Research Institute UK, London, United Kingdom; UCL Cancer Institute 
      and NIHR UCLH Clinical Research Facility, University College London Hospitals, 
      London, United Kingdom.
FAU - Italiano, A
AU  - Italiano A
AD  - Early Phase Trials and Sarcoma Units, Institut Bergonie, Bordeaux, France.
FAU - Mak, G
AU  - Mak G
AD  - Sarah Cannon Research Institute UK, London, United Kingdom.
FAU - Toulmonde, M
AU  - Toulmonde M
AD  - Early Phase Trials and Sarcoma Units, Institut Bergonie, Bordeaux, France.
FAU - Baird, R D
AU  - Baird RD
AD  - Breast Cancer Research and Early Phase Trials Teams, Cancer Research UK Cambridge 
      Centre, Cambridge, United Kingdom.
FAU - Garcia-Corbacho, J
AU  - Garcia-Corbacho J
AD  - Breast Cancer Research and Early Phase Trials Teams, Cancer Research UK Cambridge 
      Centre, Cambridge, United Kingdom.
FAU - Plummer, R
AU  - Plummer R
AD  - Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne 
      and Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, Newcastle 
      upon Tyne, United Kingdom.
FAU - Flynn, M
AU  - Flynn M
AD  - UCL Cancer Institute and NIHR UCLH Clinical Research Facility, University College 
      London Hospitals, London, United Kingdom.
FAU - Forster, M
AU  - Forster M
AD  - UCL Cancer Institute and NIHR UCLH Clinical Research Facility, University College 
      London Hospitals, London, United Kingdom.
FAU - Wilson, R H
AU  - Wilson RH
AD  - Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, 
      United Kingdom and Northern Ireland Cancer Center, Belfast City Hospital, 
      Belfast, United Kingdom.
FAU - Tosi, D
AU  - Tosi D
AD  - Early Clinical Trial Unit, Institut Regional Du Cancer de Montpellier (ICM), 
      Montpellier, France.
FAU - Adenis, A
AU  - Adenis A
AD  - Department of Medical Oncology, Centre Oscar Lambret, Lille, France.
FAU - Donaldson, K
AU  - Donaldson K
AD  - Shionogi & Co., Ltd., Osaka, Japan.
FAU - Posner, J
AU  - Posner J
AD  - Shionogi & Co., Ltd., Osaka, Japan.
FAU - Kawabata, I
AU  - Kawabata I
AD  - Shionogi & Co., Ltd., Osaka, Japan.
FAU - Arimura, A
AU  - Arimura A
AD  - Shionogi & Co., Ltd., Osaka, Japan.
FAU - Deva, S
AU  - Deva S
AD  - School of Cancer and Pharmaceutical Sciences, King's College London, Guy's 
      Hospital, London, United Kingdom.
FAU - Spicer, J
AU  - Spicer J
AD  - School of Cancer and Pharmaceutical Sciences, King's College London, Guy's 
      Hospital, London, United Kingdom. Electronic address: james.spicer@kcl.ac.uk.
LA  - eng
SI  - EudraCT/2009-017817-31
GR  - Department of Health/United Kingdom
GR  - Cancer Research UK/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180906
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 0 (S-222611)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/pathology
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Quinazolines/pharmacology/*therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - EGFR
OT  - Epertinib
OT  - HER2
OT  - S-222611
OT  - Tyrosine kinase inhibitor
EDAT- 2018/09/10 06:00
MHDA- 2019/05/21 06:00
CRDT- 2018/09/10 06:00
PHST- 2018/05/13 00:00 [received]
PHST- 2018/07/23 00:00 [revised]
PHST- 2018/07/24 00:00 [accepted]
PHST- 2018/09/10 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2018/09/10 06:00 [entrez]
AID - S0959-8049(18)31115-8 [pii]
AID - 10.1016/j.ejca.2018.07.134 [doi]
PST - ppublish
SO  - Eur J Cancer. 2018 Nov;103:17-23. doi: 10.1016/j.ejca.2018.07.134. Epub 2018 Sep 
      6.