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Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients
BACKGROUND: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes. METHODS: A cohort of patients with EGFR mutant advanced NSCLC was ide...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800294/ https://www.ncbi.nlm.nih.gov/pubmed/26889973 http://dx.doi.org/10.1038/bjc.2016.22 |
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author | Martin, Petra Shiau, Carolyn J Pasic, Maria Tsao, Ming Kamel-Reid, Suzanne Lin, Stephanie Tudor, Roxana Cheng, Susanna Higgins, Brian Burkes, Ronald Ng, Matilda Arif, Saroosh Ellis, Peter M Hubay, Stacy Kuruvilla, Sara Laurie, Scott A Li, Jing Hwang, David Lau, Anthea Shepherd, Frances A Le, Lisa W Leighl, Natasha B |
author_facet | Martin, Petra Shiau, Carolyn J Pasic, Maria Tsao, Ming Kamel-Reid, Suzanne Lin, Stephanie Tudor, Roxana Cheng, Susanna Higgins, Brian Burkes, Ronald Ng, Matilda Arif, Saroosh Ellis, Peter M Hubay, Stacy Kuruvilla, Sara Laurie, Scott A Li, Jing Hwang, David Lau, Anthea Shepherd, Frances A Le, Lisa W Leighl, Natasha B |
author_sort | Martin, Petra |
collection | PubMed |
description | BACKGROUND: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes. METHODS: A cohort of patients with EGFR mutant advanced NSCLC was identified (N=293); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association. RESULTS: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI=1.21–2.07, P=0.0008), longer TTF (hazard ratio 0.80, 95% CI=0.68–0.92, P=0.003) and better OS (hazard ratio 0.81, 95% CI=0.67–0.99, P=0.04). However, even in patients with ⩽5% mutation fraction, response rate was 34%. Females had longer TTF (P=0.02). CONCLUSIONS: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. |
format | Online Article Text |
id | pubmed-4800294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48002942017-03-15 Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients Martin, Petra Shiau, Carolyn J Pasic, Maria Tsao, Ming Kamel-Reid, Suzanne Lin, Stephanie Tudor, Roxana Cheng, Susanna Higgins, Brian Burkes, Ronald Ng, Matilda Arif, Saroosh Ellis, Peter M Hubay, Stacy Kuruvilla, Sara Laurie, Scott A Li, Jing Hwang, David Lau, Anthea Shepherd, Frances A Le, Lisa W Leighl, Natasha B Br J Cancer Clinical Study BACKGROUND: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes. METHODS: A cohort of patients with EGFR mutant advanced NSCLC was identified (N=293); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association. RESULTS: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI=1.21–2.07, P=0.0008), longer TTF (hazard ratio 0.80, 95% CI=0.68–0.92, P=0.003) and better OS (hazard ratio 0.81, 95% CI=0.67–0.99, P=0.04). However, even in patients with ⩽5% mutation fraction, response rate was 34%. Females had longer TTF (P=0.02). CONCLUSIONS: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. Nature Publishing Group 2016-03-15 2016-02-18 /pmc/articles/PMC4800294/ /pubmed/26889973 http://dx.doi.org/10.1038/bjc.2016.22 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Clinical Study Martin, Petra Shiau, Carolyn J Pasic, Maria Tsao, Ming Kamel-Reid, Suzanne Lin, Stephanie Tudor, Roxana Cheng, Susanna Higgins, Brian Burkes, Ronald Ng, Matilda Arif, Saroosh Ellis, Peter M Hubay, Stacy Kuruvilla, Sara Laurie, Scott A Li, Jing Hwang, David Lau, Anthea Shepherd, Frances A Le, Lisa W Leighl, Natasha B Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients |
title | Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients |
title_full | Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients |
title_fullStr | Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients |
title_full_unstemmed | Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients |
title_short | Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients |
title_sort | clinical impact of mutation fraction in epidermal growth factor receptor mutation positive nsclc patients |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800294/ https://www.ncbi.nlm.nih.gov/pubmed/26889973 http://dx.doi.org/10.1038/bjc.2016.22 |
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