PMID- 37760942
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231003
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 9
DP  - 2023 Sep 10
TI  - A Prospective Cohort Study Assessing the Relationship between Plasma Levels of 
      Osimertinib and Treatment Efficacy and Safety.
LID - 10.3390/biomedicines11092501 [doi]
LID - 2501
AB  - Osimertinib is a standard treatment for patients with EGFR-mutated non-small cell 
      lung carcinoma (NSCLC). We evaluated the relationship between plasma osimertinib 
      concentrations and treatment outcome in patients with NSCLC for this cohort 
      study. The plasma levels of osimertinib and its metabolite AZ5104 were measured a 
      week after the start of treatment (P1). The primary endpoint was to evaluate the 
      correlation between plasma concentration and adverse events (AEs). The 
      correlation with treatment efficacy was one of the secondary endpoints. In 
      patients with CNS metastases, the concentration in the cerebrospinal fluid was 
      also measured. Forty-one patients were enrolled. The frequency of AEs was highest 
      for rash, followed by anorexia and thrombocytopenia. Thirty-eight cases provided 
      measurements for P1. The median plasma concentration of osimertinib was 227 
      ng/mL, and that of AZ5104 was 16.5 ng/mL. The mean CNS penetration rate of two 
      cases was 3.8%. The P1 in the group with anorexia was significantly higher than 
      that in the group without anorexia (385.0 ng/mL vs. 231.5 ng/mL, p = 0.009). 
      Divided into quartiles by P1 trough level, Q2 + Q3 (164-338 ng/mL) had longer 
      PFS, while Q1 and Q4 had shorter PFS. An appropriate plasma level of osimertinib 
      may avoid some adverse events and induce long PFS. Further large-scale trials are 
      warranted.
FAU - Fukuhara, Tatsuro
AU  - Fukuhara T
AUID- ORCID: 0000-0003-0440-470X
AD  - Department of Respiratory Medicine, Miyagi Cancer Center, Natori 981-1239, Japan.
FAU - Imai, Kazuhiro
AU  - Imai K
AUID- ORCID: 0000-0003-4490-7862
AD  - Department of Thoracic Surgery, Akita University Graduate School of Medicine, 
      Akita 010-8543, Japan.
FAU - Nakagawa, Taku
AU  - Nakagawa T
AD  - Department of Thoracic Surgery, Omagari Kosei Medical Center, Daisen 014-0027, 
      Japan.
FAU - Igusa, Ryotaro
AU  - Igusa R
AD  - Department of Respiratory Medicine, Osaki Citizen Hospital, Osaki 989-6136, 
      Japan.
FAU - Yokota, Hayato
AU  - Yokota H
AUID- ORCID: 0000-0003-1389-435X
AD  - Department of Pharmacy, Akita University Hospital, Akita 010-8543, Japan.
FAU - Watanabe, Kana
AU  - Watanabe K
AD  - Department of Respiratory Medicine, Miyagi Cancer Center, Natori 981-1239, Japan.
FAU - Suzuki, Aya
AU  - Suzuki A
AD  - Department of Respiratory Medicine, Miyagi Cancer Center, Natori 981-1239, Japan.
FAU - Morita, Mami
AU  - Morita M
AD  - Department of Respiratory Medicine, Miyagi Cancer Center, Natori 981-1239, Japan.
FAU - Onodera, Ren
AU  - Onodera R
AD  - Division of Pulmonary Medicine, Department of Internal Medicine, Iwate Medical 
      University School of Medicine, Yahaba 028-3694, Japan.
FAU - Inoue, Akira
AU  - Inoue A
AD  - Department of Palliative Medicine, Tohoku University Graduate School of Medicine, 
      Sendai 980-8575, Japan.
FAU - Miura, Masatomo
AU  - Miura M
AUID- ORCID: 0000-0001-7120-2425
AD  - Department of Pharmacokinetics, Akita University Graduate School of Medicine, 
      Akita 010-8543, Japan.
FAU - Minamiya, Yoshihiro
AU  - Minamiya Y
AD  - Department of Thoracic Surgery, Akita University Graduate School of Medicine, 
      Akita 010-8543, Japan.
FAU - Maemondo, Makoto
AU  - Maemondo M
AUID- ORCID: 0000-0002-1950-1943
AD  - Division of Pulmonary Medicine, Department of Medicine, Jichi Medial University, 
      Shimotsuke 329-0498, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230910
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10526408
OTO - NOTNLM
OT  - EGFR
OT  - non-small cell lung cancer
OT  - osimertinib
OT  - trough level
COIS- Tatsuro Fukuhara has received research grants from AstraZeneca. Taku Nakagawa, 
      Akira Inoue, and Makoto Maemondo have received a speaker honorarium from 
      AstraZeneca. The remaining authors have declared no conflicts of interest.
EDAT- 2023/09/28 06:42
MHDA- 2023/09/28 06:43
PMCR- 2023/09/10
CRDT- 2023/09/28 01:09
PHST- 2023/08/10 00:00 [received]
PHST- 2023/09/07 00:00 [revised]
PHST- 2023/09/08 00:00 [accepted]
PHST- 2023/09/28 06:43 [medline]
PHST- 2023/09/28 06:42 [pubmed]
PHST- 2023/09/28 01:09 [entrez]
PHST- 2023/09/10 00:00 [pmc-release]
AID - biomedicines11092501 [pii]
AID - biomedicines-11-02501 [pii]
AID - 10.3390/biomedicines11092501 [doi]
PST - epublish
SO  - Biomedicines. 2023 Sep 10;11(9):2501. doi: 10.3390/biomedicines11092501.