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Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer

PURPOSE: Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non–small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with action...

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Autores principales: Dagogo-Jack, Ibiayi, Azzolli, Christopher G., Fintelmann, Florian, Mino-Kenudson, Mari, Farago, Anna F., Gainor, Justin F., Jiang, Ginger, Piotrowska, Zofia, Heist, Rebecca S., Lennes, Inga T., Temel, Jennifer S., Mooradian, Meghan J., Lin, Jessica J., Digumarthy, Subba R., Batten, Julie M., Robinson, Hayley, Nose, Vania, Rivera, Miguel, Nardi, Valentina, Dias-Santagata, Dora, Le, Long P., Sequist, Lecia V., Pitman, Martha, Shepard, Jo-Anne O., Shaw, Alice T., Iafrate, A. John, Lennerz, Jochen K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Clinical Oncology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200882/
https://www.ncbi.nlm.nih.gov/pubmed/30370396
http://dx.doi.org/10.1200/PO.17.00299
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author Dagogo-Jack, Ibiayi
Azzolli, Christopher G.
Fintelmann, Florian
Mino-Kenudson, Mari
Farago, Anna F.
Gainor, Justin F.
Jiang, Ginger
Piotrowska, Zofia
Heist, Rebecca S.
Lennes, Inga T.
Temel, Jennifer S.
Mooradian, Meghan J.
Lin, Jessica J.
Digumarthy, Subba R.
Batten, Julie M.
Robinson, Hayley
Nose, Vania
Rivera, Miguel
Nardi, Valentina
Dias-Santagata, Dora
Le, Long P.
Sequist, Lecia V.
Pitman, Martha
Shepard, Jo-Anne O.
Shaw, Alice T.
Iafrate, A. John
Lennerz, Jochen K.
author_facet Dagogo-Jack, Ibiayi
Azzolli, Christopher G.
Fintelmann, Florian
Mino-Kenudson, Mari
Farago, Anna F.
Gainor, Justin F.
Jiang, Ginger
Piotrowska, Zofia
Heist, Rebecca S.
Lennes, Inga T.
Temel, Jennifer S.
Mooradian, Meghan J.
Lin, Jessica J.
Digumarthy, Subba R.
Batten, Julie M.
Robinson, Hayley
Nose, Vania
Rivera, Miguel
Nardi, Valentina
Dias-Santagata, Dora
Le, Long P.
Sequist, Lecia V.
Pitman, Martha
Shepard, Jo-Anne O.
Shaw, Alice T.
Iafrate, A. John
Lennerz, Jochen K.
author_sort Dagogo-Jack, Ibiayi
collection PubMed
description PURPOSE: Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non–small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with actionable EGFR mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)–directed therapy. PATIENTS AND METHODS: We performed rapid testing for EGFR L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an EGFR-specific assay (rapid test). To determine clinical utility, we assessed concordance with NGS results, turnaround time, and TTI of EGFR therapy, and we evaluated reimbursement data. RESULTS: Between January 2015 and September 2017, we performed 243 rapid EGFR tests and identified EGFR mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid EGFR polymerase chain reaction assay were 98% and 100%, respectively. The median turnaround time for NGS was 14 days, compared with 7 days for rapid testing (P < .001). In the rapid group, 95% of patients received an EGFR inhibitor in the first-line setting. The median TTI of EGFR therapy was significantly shorter in the rapid cohort when compared with 121 historical cases (22 v 37 days; P = .01). Escalation of the initiative into an interdisciplinary ultra-rapid next-day frozen-section workflow for highly symptomatic patients (n = 8) resulted in a reduction in the median (± standard deviation) turnaround time to 1 ± 0.4 days and allowed several patients to initiate therapy within 1 week of biopsy. An extended 9-month clinical evaluation phase confirmed operational sustainability (turnaround times: ultra-rapid, 0.81 ± 0.4 days; rapid, 3 ± 1.5 days), and a 63% reimbursement rate indicated financial sustainability. CONCLUSION: Rapid genotyping facilitates earlier initiation of EGFR-directed therapies without compromising NGS workflows.
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spelling pubmed-62008822018-10-25 Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer Dagogo-Jack, Ibiayi Azzolli, Christopher G. Fintelmann, Florian Mino-Kenudson, Mari Farago, Anna F. Gainor, Justin F. Jiang, Ginger Piotrowska, Zofia Heist, Rebecca S. Lennes, Inga T. Temel, Jennifer S. Mooradian, Meghan J. Lin, Jessica J. Digumarthy, Subba R. Batten, Julie M. Robinson, Hayley Nose, Vania Rivera, Miguel Nardi, Valentina Dias-Santagata, Dora Le, Long P. Sequist, Lecia V. Pitman, Martha Shepard, Jo-Anne O. Shaw, Alice T. Iafrate, A. John Lennerz, Jochen K. JCO Precis Oncol Original Report PURPOSE: Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non–small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with actionable EGFR mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)–directed therapy. PATIENTS AND METHODS: We performed rapid testing for EGFR L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an EGFR-specific assay (rapid test). To determine clinical utility, we assessed concordance with NGS results, turnaround time, and TTI of EGFR therapy, and we evaluated reimbursement data. RESULTS: Between January 2015 and September 2017, we performed 243 rapid EGFR tests and identified EGFR mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid EGFR polymerase chain reaction assay were 98% and 100%, respectively. The median turnaround time for NGS was 14 days, compared with 7 days for rapid testing (P < .001). In the rapid group, 95% of patients received an EGFR inhibitor in the first-line setting. The median TTI of EGFR therapy was significantly shorter in the rapid cohort when compared with 121 historical cases (22 v 37 days; P = .01). Escalation of the initiative into an interdisciplinary ultra-rapid next-day frozen-section workflow for highly symptomatic patients (n = 8) resulted in a reduction in the median (± standard deviation) turnaround time to 1 ± 0.4 days and allowed several patients to initiate therapy within 1 week of biopsy. An extended 9-month clinical evaluation phase confirmed operational sustainability (turnaround times: ultra-rapid, 0.81 ± 0.4 days; rapid, 3 ± 1.5 days), and a 63% reimbursement rate indicated financial sustainability. CONCLUSION: Rapid genotyping facilitates earlier initiation of EGFR-directed therapies without compromising NGS workflows. American Society of Clinical Oncology 2018-07-24 /pmc/articles/PMC6200882/ /pubmed/30370396 http://dx.doi.org/10.1200/PO.17.00299 Text en © 2018 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Report
Dagogo-Jack, Ibiayi
Azzolli, Christopher G.
Fintelmann, Florian
Mino-Kenudson, Mari
Farago, Anna F.
Gainor, Justin F.
Jiang, Ginger
Piotrowska, Zofia
Heist, Rebecca S.
Lennes, Inga T.
Temel, Jennifer S.
Mooradian, Meghan J.
Lin, Jessica J.
Digumarthy, Subba R.
Batten, Julie M.
Robinson, Hayley
Nose, Vania
Rivera, Miguel
Nardi, Valentina
Dias-Santagata, Dora
Le, Long P.
Sequist, Lecia V.
Pitman, Martha
Shepard, Jo-Anne O.
Shaw, Alice T.
Iafrate, A. John
Lennerz, Jochen K.
Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer
title Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer
title_full Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer
title_fullStr Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer
title_full_unstemmed Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer
title_short Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer
title_sort clinical utility of rapid egfr genotyping in advanced lung cancer
topic Original Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200882/
https://www.ncbi.nlm.nih.gov/pubmed/30370396
http://dx.doi.org/10.1200/PO.17.00299
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