Cargando…
A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy
BACKGROUND: Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460863/ https://www.ncbi.nlm.nih.gov/pubmed/28586388 http://dx.doi.org/10.1371/journal.pone.0179170 |
_version_ | 1783242245595463680 |
---|---|
author | Weiss, Glen J. Byron, Sara A. Aldrich, Jessica Sangal, Ashish Barilla, Heather Kiefer, Jeffrey A. Carpten, John D. Craig, David W. Whitsett, Timothy G. |
author_facet | Weiss, Glen J. Byron, Sara A. Aldrich, Jessica Sangal, Ashish Barilla, Heather Kiefer, Jeffrey A. Carpten, John D. Craig, David W. Whitsett, Timothy G. |
author_sort | Weiss, Glen J. |
collection | PubMed |
description | BACKGROUND: Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. METHODS: Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. CONCLUSIONS: Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes. |
format | Online Article Text |
id | pubmed-5460863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54608632017-06-15 A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy Weiss, Glen J. Byron, Sara A. Aldrich, Jessica Sangal, Ashish Barilla, Heather Kiefer, Jeffrey A. Carpten, John D. Craig, David W. Whitsett, Timothy G. PLoS One Research Article BACKGROUND: Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. METHODS: Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. CONCLUSIONS: Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes. Public Library of Science 2017-06-06 /pmc/articles/PMC5460863/ /pubmed/28586388 http://dx.doi.org/10.1371/journal.pone.0179170 Text en © 2017 Weiss et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Weiss, Glen J. Byron, Sara A. Aldrich, Jessica Sangal, Ashish Barilla, Heather Kiefer, Jeffrey A. Carpten, John D. Craig, David W. Whitsett, Timothy G. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
title | A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
title_full | A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
title_fullStr | A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
title_full_unstemmed | A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
title_short | A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
title_sort | prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460863/ https://www.ncbi.nlm.nih.gov/pubmed/28586388 http://dx.doi.org/10.1371/journal.pone.0179170 |
work_keys_str_mv | AT weissglenj aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT byronsaraa aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT aldrichjessica aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT sangalashish aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT barillaheather aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT kieferjeffreya aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT carptenjohnd aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT craigdavidw aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT whitsetttimothyg aprospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT weissglenj prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT byronsaraa prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT aldrichjessica prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT sangalashish prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT barillaheather prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT kieferjeffreya prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT carptenjohnd prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT craigdavidw prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy AT whitsetttimothyg prospectivepilotstudyofgenomewideexomeandtranscriptomeprofilinginpatientswithsmallcelllungcancerprogressingafterfirstlinetherapy |