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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10526408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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