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A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety

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 AZ...

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Autores principales: Fukuhara, Tatsuro, Imai, Kazuhiro, Nakagawa, Taku, Igusa, Ryotaro, Yokota, Hayato, Watanabe, Kana, Suzuki, Aya, Morita, Mami, Onodera, Ren, Inoue, Akira, Miura, Masatomo, Minamiya, Yoshihiro, Maemondo, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526408/
https://www.ncbi.nlm.nih.gov/pubmed/37760942
http://dx.doi.org/10.3390/biomedicines11092501
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author Fukuhara, Tatsuro
Imai, Kazuhiro
Nakagawa, Taku
Igusa, Ryotaro
Yokota, Hayato
Watanabe, Kana
Suzuki, Aya
Morita, Mami
Onodera, Ren
Inoue, Akira
Miura, Masatomo
Minamiya, Yoshihiro
Maemondo, Makoto
author_facet Fukuhara, Tatsuro
Imai, Kazuhiro
Nakagawa, Taku
Igusa, Ryotaro
Yokota, Hayato
Watanabe, Kana
Suzuki, Aya
Morita, Mami
Onodera, Ren
Inoue, Akira
Miura, Masatomo
Minamiya, Yoshihiro
Maemondo, Makoto
author_sort Fukuhara, Tatsuro
collection PubMed
description 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.
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spelling pubmed-105264082023-09-28 A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety Fukuhara, Tatsuro Imai, Kazuhiro Nakagawa, Taku Igusa, Ryotaro Yokota, Hayato Watanabe, Kana Suzuki, Aya Morita, Mami Onodera, Ren Inoue, Akira Miura, Masatomo Minamiya, Yoshihiro Maemondo, Makoto Biomedicines Article 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. MDPI 2023-09-10 /pmc/articles/PMC10526408/ /pubmed/37760942 http://dx.doi.org/10.3390/biomedicines11092501 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fukuhara, Tatsuro
Imai, Kazuhiro
Nakagawa, Taku
Igusa, Ryotaro
Yokota, Hayato
Watanabe, Kana
Suzuki, Aya
Morita, Mami
Onodera, Ren
Inoue, Akira
Miura, Masatomo
Minamiya, Yoshihiro
Maemondo, Makoto
A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety
title A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety
title_full A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety
title_fullStr A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety
title_full_unstemmed A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety
title_short A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety
title_sort prospective cohort study assessing the relationship between plasma levels of osimertinib and treatment efficacy and safety
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526408/
https://www.ncbi.nlm.nih.gov/pubmed/37760942
http://dx.doi.org/10.3390/biomedicines11092501
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