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Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer
BACKGROUND: Epidermal growth factor receptor-mutated (EGFR(+)) non-small-cell lung cancer (NSCLC) patients failing tyrosine kinase inhibitors (TKI) can benefit from next-line targeted therapies, but implementation is challenging. METHODS: EGFR(+) NSCLC patients treated with first/second-generation (...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366107/ https://www.ncbi.nlm.nih.gov/pubmed/34408792 http://dx.doi.org/10.1177/1758835921996509 |
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author | Magios, Nikolaus Bozorgmehr, Farastuk Volckmar, Anna-Lena Kazdal, Daniel Kirchner, Martina Herth, Felix J. Heussel, Claus-Peter Eichhorn, Florian Meister, Michael Muley, Thomas Elshafie, Rami A. Fischer, Jürgen R. Faehling, Martin Kriegsmann, Mark Schirmacher, Peter Bischoff, Helge Stenzinger, Albrecht Thomas, Michael Christopoulos, Petros |
author_facet | Magios, Nikolaus Bozorgmehr, Farastuk Volckmar, Anna-Lena Kazdal, Daniel Kirchner, Martina Herth, Felix J. Heussel, Claus-Peter Eichhorn, Florian Meister, Michael Muley, Thomas Elshafie, Rami A. Fischer, Jürgen R. Faehling, Martin Kriegsmann, Mark Schirmacher, Peter Bischoff, Helge Stenzinger, Albrecht Thomas, Michael Christopoulos, Petros |
author_sort | Magios, Nikolaus |
collection | PubMed |
description | BACKGROUND: Epidermal growth factor receptor-mutated (EGFR(+)) non-small-cell lung cancer (NSCLC) patients failing tyrosine kinase inhibitors (TKI) can benefit from next-line targeted therapies, but implementation is challenging. METHODS: EGFR(+) NSCLC patients treated with first/second-generation (1G/2G) TKI at our institution with a last follow-up after osimertinib approval (February 2016), were analyzed retrospectively, and the results compared with published data under osimertinib. RESULTS: A total of 207 patients received erlotinib (37%), gefitinib (16%) or afatinib (47%). The median age was 66 years, with a predominance of female (70%), never/light-smokers (69%). T790M testing was performed in 174/202 progressive cases (86%), positive in 93/174 (53%), and followed by osimertinib in 87/93 (94%). Among the 135 deceased patients, 94 (70%) received subsequent systemic treatment (43% chemotherapy, 39% osimertinib), while 30% died without, either before (4%) or after progression, due to rapid clinical deterioration (22%), patient refusal of further therapy (2%), or severe competing illness (2%). Lack of subsequent treatment was significantly (4.5x, p < 0.001) associated with lack of T790M testing, whose most frequent cause (in approximately 50% of cases) was also rapid clinical decline. Among the 127 consecutive patients with failure of 1G/2G TKI started after November 2015, 47 (37%) received osimertinib, with a median overall survival of 36 months versus 24 and 21 months for patients with alternative and no subsequent therapies (p = 0.003). CONCLUSION: Osimertinib after 1G/2G TKI failure prolongs survival, but approximately 15% and 30% of patients forego molecular retesting and subsequent treatment, respectively, mainly due to rapid clinical deterioration. This is an important remediable obstacle to sequential TKI treatment for EGFR(+) NSCLC. It pertains also to other actionable resistance mechanisms emerging under 1G/2G inhibitors or osimertinib, whose rate for lack of next-line therapy is similar (approximately 35% in the FLAURA/AURA3 trials), and highlights the need for closer monitoring alongside broader profiling of TKI-treated EGFR(+) NSCLC in the future. |
format | Online Article Text |
id | pubmed-8366107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-83661072021-08-17 Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer Magios, Nikolaus Bozorgmehr, Farastuk Volckmar, Anna-Lena Kazdal, Daniel Kirchner, Martina Herth, Felix J. Heussel, Claus-Peter Eichhorn, Florian Meister, Michael Muley, Thomas Elshafie, Rami A. Fischer, Jürgen R. Faehling, Martin Kriegsmann, Mark Schirmacher, Peter Bischoff, Helge Stenzinger, Albrecht Thomas, Michael Christopoulos, Petros Ther Adv Med Oncol Original Research BACKGROUND: Epidermal growth factor receptor-mutated (EGFR(+)) non-small-cell lung cancer (NSCLC) patients failing tyrosine kinase inhibitors (TKI) can benefit from next-line targeted therapies, but implementation is challenging. METHODS: EGFR(+) NSCLC patients treated with first/second-generation (1G/2G) TKI at our institution with a last follow-up after osimertinib approval (February 2016), were analyzed retrospectively, and the results compared with published data under osimertinib. RESULTS: A total of 207 patients received erlotinib (37%), gefitinib (16%) or afatinib (47%). The median age was 66 years, with a predominance of female (70%), never/light-smokers (69%). T790M testing was performed in 174/202 progressive cases (86%), positive in 93/174 (53%), and followed by osimertinib in 87/93 (94%). Among the 135 deceased patients, 94 (70%) received subsequent systemic treatment (43% chemotherapy, 39% osimertinib), while 30% died without, either before (4%) or after progression, due to rapid clinical deterioration (22%), patient refusal of further therapy (2%), or severe competing illness (2%). Lack of subsequent treatment was significantly (4.5x, p < 0.001) associated with lack of T790M testing, whose most frequent cause (in approximately 50% of cases) was also rapid clinical decline. Among the 127 consecutive patients with failure of 1G/2G TKI started after November 2015, 47 (37%) received osimertinib, with a median overall survival of 36 months versus 24 and 21 months for patients with alternative and no subsequent therapies (p = 0.003). CONCLUSION: Osimertinib after 1G/2G TKI failure prolongs survival, but approximately 15% and 30% of patients forego molecular retesting and subsequent treatment, respectively, mainly due to rapid clinical deterioration. This is an important remediable obstacle to sequential TKI treatment for EGFR(+) NSCLC. It pertains also to other actionable resistance mechanisms emerging under 1G/2G inhibitors or osimertinib, whose rate for lack of next-line therapy is similar (approximately 35% in the FLAURA/AURA3 trials), and highlights the need for closer monitoring alongside broader profiling of TKI-treated EGFR(+) NSCLC in the future. SAGE Publications 2021-03-24 /pmc/articles/PMC8366107/ /pubmed/34408792 http://dx.doi.org/10.1177/1758835921996509 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Magios, Nikolaus Bozorgmehr, Farastuk Volckmar, Anna-Lena Kazdal, Daniel Kirchner, Martina Herth, Felix J. Heussel, Claus-Peter Eichhorn, Florian Meister, Michael Muley, Thomas Elshafie, Rami A. Fischer, Jürgen R. Faehling, Martin Kriegsmann, Mark Schirmacher, Peter Bischoff, Helge Stenzinger, Albrecht Thomas, Michael Christopoulos, Petros Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer |
title | Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer |
title_full | Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer |
title_fullStr | Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer |
title_full_unstemmed | Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer |
title_short | Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer |
title_sort | real-world implementation of sequential targeted therapies for egfr-mutated lung cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366107/ https://www.ncbi.nlm.nih.gov/pubmed/34408792 http://dx.doi.org/10.1177/1758835921996509 |
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