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Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study
SIMPLE SUMMARY: Patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer can have central nervous system (CNS) metastases during their disease course. A high unmet medical need exists especially for patients with T790M-positive NSCLC whose disease progressed...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345213/ https://www.ncbi.nlm.nih.gov/pubmed/34359582 http://dx.doi.org/10.3390/cancers13153681 |
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author | Ahn, Beung-Chul Kim, Jee Hung Pyo, Kyoung-Ho Lim, Sun Min Hong, Min Hee Kim, Hye Ryun Cho, Byoung Chul |
author_facet | Ahn, Beung-Chul Kim, Jee Hung Pyo, Kyoung-Ho Lim, Sun Min Hong, Min Hee Kim, Hye Ryun Cho, Byoung Chul |
author_sort | Ahn, Beung-Chul |
collection | PubMed |
description | SIMPLE SUMMARY: Patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer can have central nervous system (CNS) metastases during their disease course. A high unmet medical need exists especially for patients with T790M-positive NSCLC whose disease progressed after first-line EGFR-TKI. Osimertinib is a third-generation EGFR-TKI with selective activity for both sensitizing and EGFR T790M mutations and has improved CNS activity over first- and second-generation EGFR TKIs and chemotherapies. This study confirmed the clinical activity and CNS efficacy of osimertinib in an unselected real-world population. ABSTRACT: Up to 40% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) may develop central nervous system (CNS) metastases throughout their disease. Moreover, the first- and second-generation EGFR-tyrosine kinase inhibitors have limited efficacy because of their poor blood–brain barrier permeability. Therefore, we conducted preplanned analyses of ASTRIS, a clinical study of the third-generation EGFR-TKI osimertinib to demonstrate its potential role in intracranial response efficacies. We retrospectively examined 89 NSCLC patients with brain evaluation who were not amenable to curative surgery or radiotherapy and received osimertinib upon confirmation of the presence of the T790M mutation. We collected the information regarding patients’ baseline characteristics, baseline intracranial status, including leptomeningeal metastases (LM), and intracranial responses measured by Response Evaluation Criteria in Solid Tumors version 1.1, using independent central review. The median age was 60 years, and 69.7% of the patients were female. Sixty-five patients (73.0%) had brain metastases (BM) at baseline and nineteen patients (23.5%) had additional LM. Among patients with brain metastases, 24 (36.9%) had ≥1 measurable brain metastases and 16 were evaluated for the objective response. In the CNS evaluable for response set, the intracranial objective response rate (cORR) and disease control rate (cDCR) were 62.5% (95% confidence interval (CI), 38.3–82.6%) and 93.8% (95% CI, 74.3–99.3%), respectively. The median intracranial progression-free survival (cPFS) was 13.0 (95% CI, 7.21–18.8) months, including patients with measurable and non-measurable BM or LM. Our cORR, cDCR, and cPFS were comparable to those observed in previous clinical trials. The outcome of this study helps to demonstrate the potential role of intracranial efficacies of osimertinib 80 mg administration in T790M-positive advanced NSCLC with/without BM or LM. |
format | Online Article Text |
id | pubmed-8345213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83452132021-08-07 Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study Ahn, Beung-Chul Kim, Jee Hung Pyo, Kyoung-Ho Lim, Sun Min Hong, Min Hee Kim, Hye Ryun Cho, Byoung Chul Cancers (Basel) Article SIMPLE SUMMARY: Patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer can have central nervous system (CNS) metastases during their disease course. A high unmet medical need exists especially for patients with T790M-positive NSCLC whose disease progressed after first-line EGFR-TKI. Osimertinib is a third-generation EGFR-TKI with selective activity for both sensitizing and EGFR T790M mutations and has improved CNS activity over first- and second-generation EGFR TKIs and chemotherapies. This study confirmed the clinical activity and CNS efficacy of osimertinib in an unselected real-world population. ABSTRACT: Up to 40% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) may develop central nervous system (CNS) metastases throughout their disease. Moreover, the first- and second-generation EGFR-tyrosine kinase inhibitors have limited efficacy because of their poor blood–brain barrier permeability. Therefore, we conducted preplanned analyses of ASTRIS, a clinical study of the third-generation EGFR-TKI osimertinib to demonstrate its potential role in intracranial response efficacies. We retrospectively examined 89 NSCLC patients with brain evaluation who were not amenable to curative surgery or radiotherapy and received osimertinib upon confirmation of the presence of the T790M mutation. We collected the information regarding patients’ baseline characteristics, baseline intracranial status, including leptomeningeal metastases (LM), and intracranial responses measured by Response Evaluation Criteria in Solid Tumors version 1.1, using independent central review. The median age was 60 years, and 69.7% of the patients were female. Sixty-five patients (73.0%) had brain metastases (BM) at baseline and nineteen patients (23.5%) had additional LM. Among patients with brain metastases, 24 (36.9%) had ≥1 measurable brain metastases and 16 were evaluated for the objective response. In the CNS evaluable for response set, the intracranial objective response rate (cORR) and disease control rate (cDCR) were 62.5% (95% confidence interval (CI), 38.3–82.6%) and 93.8% (95% CI, 74.3–99.3%), respectively. The median intracranial progression-free survival (cPFS) was 13.0 (95% CI, 7.21–18.8) months, including patients with measurable and non-measurable BM or LM. Our cORR, cDCR, and cPFS were comparable to those observed in previous clinical trials. The outcome of this study helps to demonstrate the potential role of intracranial efficacies of osimertinib 80 mg administration in T790M-positive advanced NSCLC with/without BM or LM. MDPI 2021-07-22 /pmc/articles/PMC8345213/ /pubmed/34359582 http://dx.doi.org/10.3390/cancers13153681 Text en © 2021 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 Ahn, Beung-Chul Kim, Jee Hung Pyo, Kyoung-Ho Lim, Sun Min Hong, Min Hee Kim, Hye Ryun Cho, Byoung Chul Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study |
title | Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study |
title_full | Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study |
title_fullStr | Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study |
title_full_unstemmed | Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study |
title_short | Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study |
title_sort | analyses of cns response to osimertinib in patients with t790m-positive advanced nsclc from astris korean subset, open-label real-world study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345213/ https://www.ncbi.nlm.nih.gov/pubmed/34359582 http://dx.doi.org/10.3390/cancers13153681 |
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