PMID- 34862083
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20220128
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 160
DP  - 2022 Jan
TI  - Pharmacokinetic and pharmacogenomic analysis of low-dose afatinib treatment in 
      elderly patients with EGFR mutation-positive non-small cell lung cancer.
PG  - 227-234
LID - S0959-8049(21)01182-5 [pii]
LID - 10.1016/j.ejca.2021.10.024 [doi]
AB  - PURPOSE: An increasing number of advanced non-small cell lung cancer (NSCLC) 
      cases are being reported in the ageing population. However, studies on the use of 
      afatinib in elderly patients are scarce. We conducted a prospective multicentre, 
      single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use 
      in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) 
      and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters. PATIENTS AND METHODS: 
      The primary end-point was the objective response rate (ORR), and the planned 
      number of registered cases was 35, with a threshold ORR of 50%, an expected ORR 
      of 75%, alpha of 0.05, and beta of 0.1. Secondary end-points were progression-free 
      survival (PFS), overall survival (OS), the incidence rate of adverse events 
      (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady 
      state (Css) and at the occurrence of clinically significant AEs. RESULTS: The 
      median age of the patients was 79 years. The ORR was 80.0% and the disease 
      control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, 
      respectively. Four patients discontinued because of AEs. Treatment-related death 
      was not observed. No significant change in QOL was observed at baseline and after 
      4, 8, and 12 weeks. Css was comparable with those in previous reports and was 
      significantly higher in patients with grade 3 AEs. Direct correlations between 
      afatinib treatment and PGx profiles were not observed. CONCLUSIONS: An afatinib 
      starting dose of 30 mg/day could be an effective and safe treatment option for 
      elderly patients.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Mizugaki, Hidenori
AU  - Mizugaki H
AD  - Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, 
      Sapporo, Japan. Electronic address: hidenori.mizugaki@jfcr.or.jp.
FAU - Oizumi, Satoshi
AU  - Oizumi S
AD  - Department of Respiratory Medicine, National Hospital Organization Hokkaido 
      Cancer Center, Sapporo, Japan.
FAU - Fujita, Yuka
AU  - Fujita Y
AD  - Department of Respiratory Medicine, National Hospital Organization Asahikawa 
      Medical Center, Asahikawa, Japan.
FAU - Harada, Toshiyuki
AU  - Harada T
AD  - Department of Respiratory Medicine, Japan Community Health Care Organization 
      Hokkaido Hospital, Sapporo, Japan.
FAU - Nakahara, Yoshiro
AU  - Nakahara Y
AD  - Department of Respiratory Medicine, Kitasato University School of Medicine, 
      Kanagawa, Japan.
FAU - Takashina, Taichi
AU  - Takashina T
AD  - Division of Respiratory Medicine, Iwamizawa Municipal General Hospital, 
      Iwamizawa, Japan.
FAU - Ko, Ryo
AU  - Ko R
AD  - Department of Respiratory Medicine, Juntendo University Graduate School of 
      Medicine, Tokyo, Japan.
FAU - Watanabe, Kageaki
AU  - Watanabe K
AD  - Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan 
      Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
FAU - Hotta, Takamasa
AU  - Hotta T
AD  - Division of Medical Oncology and Respiratory Medicine, Department of Internal 
      Medicine, Shimane University, School of Medicine, Shimane, Japan.
FAU - Minemura, Hiroyuki
AU  - Minemura H
AD  - Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.
FAU - Saeki, Sho
AU  - Saeki S
AD  - Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, 
      Japan.
FAU - Asahina, Hajime
AU  - Asahina H
AD  - Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, 
      Sapporo, Japan.
FAU - Nakamura, Keiichi
AU  - Nakamura K
AD  - Department of Respiratory Medicine, National Hospital Organization Asahikawa 
      Medical Center, Asahikawa, Japan.
FAU - Nakamura, Hiromi
AU  - Nakamura H
AD  - Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, 
      Japan.
FAU - Hosoda, Fumie
AU  - Hosoda F
AD  - Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, 
      Japan.
FAU - Yagishita, Shigehiro
AU  - Yagishita S
AD  - Division of Molecular Pharmacology, National Cancer Center Research Institute, 
      Tokyo, Japan.
FAU - Hamada, Akinobu
AU  - Hamada A
AD  - Division of Molecular Pharmacology, National Cancer Center Research Institute, 
      Tokyo, Japan.
LA  - eng
SI  - UMIN-CTR/UMIN0000177050
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211130
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Protein Kinase Inhibitors)
RN  - 41UD74L59M (Afatinib)
SB  - IM
MH  - Afatinib/*pharmacokinetics/*pharmacology/therapeutic use
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/mortality
MH  - Male
MH  - Progression-Free Survival
MH  - Protein Kinase Inhibitors/*pharmacokinetics/*pharmacology/therapeutic use
OTO - NOTNLM
OT  - EGFR mutation
OT  - Elderly patients
OT  - Low-dose afatinib
OT  - Pharmacogenomics
OT  - Pharmacokinetics
EDAT- 2021/12/05 06:00
MHDA- 2022/01/29 06:00
CRDT- 2021/12/04 05:32
PHST- 2021/06/18 00:00 [received]
PHST- 2021/10/08 00:00 [revised]
PHST- 2021/10/24 00:00 [accepted]
PHST- 2021/12/05 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2021/12/04 05:32 [entrez]
AID - S0959-8049(21)01182-5 [pii]
AID - 10.1016/j.ejca.2021.10.024 [doi]
PST - ppublish
SO  - Eur J Cancer. 2022 Jan;160:227-234. doi: 10.1016/j.ejca.2021.10.024. Epub 2021 
      Nov 30.