PMID- 37806290
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231127
IS  - 1879-4076 (Electronic)
IS  - 1879-4068 (Linking)
VI  - 14
IP  - 8
DP  - 2023 Nov
TI  - Representation of older patients in the safety analysis of protein kinase 
      inhibitor registration studies.
PG  - 101636
LID - S1879-4068(23)00233-3 [pii]
LID - 10.1016/j.jgo.2023.101636 [doi]
AB  - INTRODUCTION: Older patients (>/=65 years old) make up the majority of the cancer 
      population. Older patients seem to experience more adverse events (AEs) from 
      protein kinase inhibitors (PKIs) in clinical practice. Yet they are 
      underrepresented in clinical trials. We aimed to evaluate whether age-related 
      safety differences were described at authorization of PKIs. Representation of 
      older patients in registration studies was also evaluated. MATERIALS AND METHODS: 
      European Public Assessment Reports (EPARs) of PKIs authorized between 2010 and 
      2015 were evaluated for the description of age-related safety- and 
      pharmacokinetic differences. The International Council for Harmonization of 
      Technical Requirement for Pharmaceuticals for Human Use (ICH) E7 guideline was 
      applied to EPARs to assess the representation of older patients. Study results 
      were presented descriptively. RESULTS: Eighteen PKIs with 19 EPARs were analyzed. 
      Age-related safety differences were described in 14 out of 19 EPARs, and 
      age-related pharmacokinetic differences in 1 out of 19 EPARs. More than 100 older 
      patients were included in half of the studies. Older patients were not excluded 
      solely by age, although other inclusion and exclusion criteria negatively 
      influenced enrollment of older patients. None of the PKIs met all criteria from 
      the ICH E7 guideline. DISCUSSION: Age-related safety differences are described 
      for most PKIs. Older patients were underrepresented in PKI registration studies. 
      Adequate representation of older patients in clinical trials for PKIs is vital, 
      since they make up most of the cancer population.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - van Kampen, Emma
AU  - van Kampen E
AD  - Department of Clinical Pharmacy and Pharmacology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the 
      Netherlands.
FAU - van Bussel, Mark T J
AU  - van Bussel MTJ
AD  - College ter Beoordeling van Geneesmiddelen, Dutch Medicines Evaluation Board 
      (CBG-MEB), Graadt van Roggenweg 500, 3531 AH Utrecht, the Netherlands.
FAU - Oude Munnink, Thijs H
AU  - Oude Munnink TH
AD  - Department of Clinical Pharmacy and Pharmacology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the 
      Netherlands.
FAU - Touw, Daan J
AU  - Touw DJ
AD  - Department of Clinical Pharmacy and Pharmacology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the 
      Netherlands.
FAU - Broekman, K Esther
AU  - Broekman KE
AD  - College ter Beoordeling van Geneesmiddelen, Dutch Medicines Evaluation Board 
      (CBG-MEB), Graadt van Roggenweg 500, 3531 AH Utrecht, the Netherlands; Department 
      of Medical Oncology, University Medical Center Groningen, University of 
      Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands. Electronic address: 
      k.e.broekman@umcg.nl.
LA  - eng
PT  - Journal Article
DEP - 20231006
PL  - Netherlands
TA  - J Geriatr Oncol
JT  - Journal of geriatric oncology
JID - 101534770
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Humans
MH  - Aged
MH  - *Protein Kinase Inhibitors/adverse effects
MH  - *Neoplasms/drug therapy
OTO - NOTNLM
OT  - Cancer
OT  - Elderly
OT  - European public assessment report
OT  - ICH E7 guideline
OT  - Protein kinase inhibitor
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2023/10/09 00:42
MHDA- 2023/11/27 12:43
CRDT- 2023/10/08 18:20
PHST- 2022/10/24 00:00 [received]
PHST- 2023/07/13 00:00 [revised]
PHST- 2023/09/19 00:00 [accepted]
PHST- 2023/11/27 12:43 [medline]
PHST- 2023/10/09 00:42 [pubmed]
PHST- 2023/10/08 18:20 [entrez]
AID - S1879-4068(23)00233-3 [pii]
AID - 10.1016/j.jgo.2023.101636 [doi]
PST - ppublish
SO  - J Geriatr Oncol. 2023 Nov;14(8):101636. doi: 10.1016/j.jgo.2023.101636. Epub 2023 
      Oct 6.