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Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors
BACKGROUND: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibit...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352023/ https://www.ncbi.nlm.nih.gov/pubmed/32753961 http://dx.doi.org/10.2147/CMAR.S253760 |
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author | Chai, Chee-Shee Liam, Chong-Kin Poh, Mau-Ern Ong, Diana Bee-Lan Pang, Yong-Kek Cheah, Phaik-Leng Ho, Gwo-Fuang Alip, Adlinda |
author_facet | Chai, Chee-Shee Liam, Chong-Kin Poh, Mau-Ern Ong, Diana Bee-Lan Pang, Yong-Kek Cheah, Phaik-Leng Ho, Gwo-Fuang Alip, Adlinda |
author_sort | Chai, Chee-Shee |
collection | PubMed |
description | BACKGROUND: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI). METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017. RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84–6.25, p = 0.104). CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations. |
format | Online Article Text |
id | pubmed-7352023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-73520232020-08-03 Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors Chai, Chee-Shee Liam, Chong-Kin Poh, Mau-Ern Ong, Diana Bee-Lan Pang, Yong-Kek Cheah, Phaik-Leng Ho, Gwo-Fuang Alip, Adlinda Cancer Manag Res Original Research BACKGROUND: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI). METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017. RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84–6.25, p = 0.104). CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations. Dove 2020-07-06 /pmc/articles/PMC7352023/ /pubmed/32753961 http://dx.doi.org/10.2147/CMAR.S253760 Text en © 2020 Chai et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Chai, Chee-Shee Liam, Chong-Kin Poh, Mau-Ern Ong, Diana Bee-Lan Pang, Yong-Kek Cheah, Phaik-Leng Ho, Gwo-Fuang Alip, Adlinda Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors |
title | Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors |
title_full | Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors |
title_fullStr | Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors |
title_full_unstemmed | Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors |
title_short | Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors |
title_sort | predictors of acquired t790m mutation in patients failing first- or second-generation epidermal growth factor receptor-tyrosine kinase inhibitors |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352023/ https://www.ncbi.nlm.nih.gov/pubmed/32753961 http://dx.doi.org/10.2147/CMAR.S253760 |
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