PMID- 38536543
OWN - NLM
STAT- Publisher
LR  - 20240327
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
DP  - 2024 Mar 27
TI  - Effect of early dose reduction of osimertinib on efficacy in the first-line 
      treatment for EGFR-mutated non-small cell lung cancer.
LID - 10.1007/s10637-024-01432-4 [doi]
AB  - Osimertinib is used as the first-line therapy for patients with epidermal growth 
      factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, early 
      dose reduction is often required due to adverse events (AEs). This study aimed to 
      evaluate the effect of early dose reduction of osimertinib on efficacy and 
      safety. This was a retrospective study including patients with EGFR-mutated NSCLC 
      who were started on osimertinib as the first-line therapy between August 2018 and 
      December 2021. Patients whose doses were reduced to less than 80 mg/day within 6 
      months of osimertinib initiation or started at 40 mg/day were defined as the dose 
      reduction group. The primary endpoint was progression-free survival (PFS). 
      Factors affecting PFS were explored using the Cox proportional hazards model. A 
      total of 85 patients were included in this study. No significant differences in 
      patient characteristics were observed between the dose reduction (n = 25) and 
      standard dose groups (n = 60). The median PFS in the dose reduction group was 
      significantly prolonged compared with that in the standard dose group (26.0 
      months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, 
      excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 
      L858R mutation, malignant pleural effusion or pleural metastasis, liver 
      metastasis, and dose reduction within 6 months were independent factors affecting 
      PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for 
      prolonging PFS in patients with EGFR-mutated NSCLC.
CI  - (c) 2024. The Author(s).
FAU - Hori, Tomoki
AU  - Hori T
AD  - Department of Pharmacy, Nara Prefecture General Medical Center, 2-897-5 
      Shichijo-nishimachi, Nara, 630-8581, Japan.
AD  - Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, 
      Kobe, 650-0017, Japan.
FAU - Yamamoto, Kazuhiro
AU  - Yamamoto K
AD  - Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, 
      Kobe, 650-0017, Japan. yamakz@med.kobe-u.ac.jp.
FAU - Ito, Takefumi
AU  - Ito T
AD  - Department of Respiratory Medicine, Nara Prefecture General Medical Center, 
      2-897-5 Shichijo-nishimachi, Nara, 630-8581, Japan.
FAU - Ikushima, Shigeki
AU  - Ikushima S
AD  - Department of Pharmacy, Nara Prefecture General Medical Center, 2-897-5 
      Shichijo-nishimachi, Nara, 630-8581, Japan.
FAU - Omura, Tomohiro
AU  - Omura T
AD  - Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, 
      Kobe, 650-0017, Japan.
FAU - Yano, Ikuko
AU  - Yano I
AD  - Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, 
      Kobe, 650-0017, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240327
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
SB  - IM
OTO - NOTNLM
OT  - Dose reduction
OT  - Epidermal growth factor receptor
OT  - Non-small cell lung cancer
OT  - Osimertinib
OT  - Progression-free survival
EDAT- 2024/03/27 18:45
MHDA- 2024/03/27 18:45
CRDT- 2024/03/27 12:20
PHST- 2023/12/29 00:00 [received]
PHST- 2024/02/20 00:00 [accepted]
PHST- 2024/03/27 18:45 [medline]
PHST- 2024/03/27 18:45 [pubmed]
PHST- 2024/03/27 12:20 [entrez]
AID - 10.1007/s10637-024-01432-4 [pii]
AID - 10.1007/s10637-024-01432-4 [doi]
PST - aheadofprint
SO  - Invest New Drugs. 2024 Mar 27. doi: 10.1007/s10637-024-01432-4.