Clinical Impact of Osimertinib Dose Reduction in the First-Line Setting on EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Retrospective Monocentric Study.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S494112

Hirokazu Iso, Makiko Yomota, Yukari Shirakura, Tadatsugu Yoshinaga, Shoko Kawai, Kosuke Narita, Masahiro Seike, Yukio Hosomi

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引用次数: 0

Abstract

Purpose: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. In the FLAURA trial, osimertinib demonstrated longer progression-free survival (PFS) and overall survival (OS) compared to gefitinib or erlotinib. In the trial, dose reductions occurred in 5% of patients, primarily due to QT prolongation. However, various adverse events can also lead to dose reductions in clinical practice, and the efficacy of osimertinib after dose reduction remains unclear. The present study was conducted to evaluate the clinical impact of osimertinib dose reduction.

Patients and methods: This monocentric retrospective study was conducted at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Ninety patients with EGFR mutation-positive non-squamous non-small-cell lung cancer receiving osimertinib as their first-line therapy between August 2018 and December 2021 were included.

Results: Of the cohort, 23 patients had an osimertinib dose reduction during their clinical course. The dose reduction group tended to have a lower median body weight and a higher proportion of elderly patients aged 80 years or older. The median PFS was 21.2 months (95% confidence interval [CI]: 8.22-34.18) in the dose reduction group and 18.6 (95% CI: 13.04-24.23) months in the regular-dose group. The median OS was 29.6 months (95% CI: 17.44-41.70) in the osimertinib dose-reduction group and 37.7 (95% CI: 27.10-48.23) months in the regular-dose group. Dose reduction did not significantly impact the time-dependent hazard ratio (HR) for PFS (HR 1.22 [95% CI: 0.55-1.89]) or OS (HR: 1.24 [95% CI: 0.64-2.42]). The adverse events leading to dose reduction were mainly rash, anorexia, and paronychia, and no fatal adverse events were observed after dose reduction.

Conclusion: The present study suggests that dose reduction may not compromise the efficacy of osimertinib. However, the clinical impact of dose reduction is not fully understood. Physicians should carefully weigh its benefits and risks before implementation.

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.