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Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution

We evaluated the preliminary efficacy and feasibility of a next-generation sequencing (NGS)-based targeted anticancer therapy in refractory solid tumors at a Korean institution. Thirty-six patients with advanced cancer underwent molecular profiling with NGS with the intent of clinical application of...

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Autores principales: Park, Hyung Soon, Lim, Sun Min, Kim, Sora, Kim, Sangwoo, Kim, Hye Ryun, Kwack, KyuBum, Lee, Min Goo, Kim, Joo-Hang, Moon, Yong Wha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841558/
https://www.ncbi.nlm.nih.gov/pubmed/27105424
http://dx.doi.org/10.1371/journal.pone.0154133
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author Park, Hyung Soon
Lim, Sun Min
Kim, Sora
Kim, Sangwoo
Kim, Hye Ryun
Kwack, KyuBum
Lee, Min Goo
Kim, Joo-Hang
Moon, Yong Wha
author_facet Park, Hyung Soon
Lim, Sun Min
Kim, Sora
Kim, Sangwoo
Kim, Hye Ryun
Kwack, KyuBum
Lee, Min Goo
Kim, Joo-Hang
Moon, Yong Wha
author_sort Park, Hyung Soon
collection PubMed
description We evaluated the preliminary efficacy and feasibility of a next-generation sequencing (NGS)-based targeted anticancer therapy in refractory solid tumors at a Korean institution. Thirty-six patients with advanced cancer underwent molecular profiling with NGS with the intent of clinical application of available matched targeted agents. Formalin-fixed paraffin-embedded (FFPE) tumors were sequenced using the Comprehensive Cancer Panel (CCP) or FoundationOne in the Clinical Laboratory Improvement Amendments-certified laboratory in the USA. Response evaluations were performed according to RECIST v1.1. Four specimens did not pass the DNA quality test and 32 specimens were successfully sequenced with CCP (n = 31) and FoundationOne (n = 1). Of the 32 sequenced patients, 10 (31.3%) were ≤40 years. Twelve patients (37.5%) had received ≥3 types of prior systemic therapies. Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease). Nineteen of 24 patients with actionable mutations could not undergo targeted therapy based on genomic testing because of declining performance status (10/24, 41.7%), stable disease with previous treatment (5/24, 20.8%), and lack of access to targeted medication (4/24, 16.7%). NGS-based targeted therapy may be a good option in selected patients with refractory solid tumors. To pursue this strategy in Korea, lack of access to clinical-grade NGS assays and a limited number of genotype-matched targeted medications needs to be addressed and resolved.
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spelling pubmed-48415582016-04-29 Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution Park, Hyung Soon Lim, Sun Min Kim, Sora Kim, Sangwoo Kim, Hye Ryun Kwack, KyuBum Lee, Min Goo Kim, Joo-Hang Moon, Yong Wha PLoS One Research Article We evaluated the preliminary efficacy and feasibility of a next-generation sequencing (NGS)-based targeted anticancer therapy in refractory solid tumors at a Korean institution. Thirty-six patients with advanced cancer underwent molecular profiling with NGS with the intent of clinical application of available matched targeted agents. Formalin-fixed paraffin-embedded (FFPE) tumors were sequenced using the Comprehensive Cancer Panel (CCP) or FoundationOne in the Clinical Laboratory Improvement Amendments-certified laboratory in the USA. Response evaluations were performed according to RECIST v1.1. Four specimens did not pass the DNA quality test and 32 specimens were successfully sequenced with CCP (n = 31) and FoundationOne (n = 1). Of the 32 sequenced patients, 10 (31.3%) were ≤40 years. Twelve patients (37.5%) had received ≥3 types of prior systemic therapies. Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease). Nineteen of 24 patients with actionable mutations could not undergo targeted therapy based on genomic testing because of declining performance status (10/24, 41.7%), stable disease with previous treatment (5/24, 20.8%), and lack of access to targeted medication (4/24, 16.7%). NGS-based targeted therapy may be a good option in selected patients with refractory solid tumors. To pursue this strategy in Korea, lack of access to clinical-grade NGS assays and a limited number of genotype-matched targeted medications needs to be addressed and resolved. Public Library of Science 2016-04-22 /pmc/articles/PMC4841558/ /pubmed/27105424 http://dx.doi.org/10.1371/journal.pone.0154133 Text en © 2016 Park 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
Park, Hyung Soon
Lim, Sun Min
Kim, Sora
Kim, Sangwoo
Kim, Hye Ryun
Kwack, KyuBum
Lee, Min Goo
Kim, Joo-Hang
Moon, Yong Wha
Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution
title Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution
title_full Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution
title_fullStr Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution
title_full_unstemmed Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution
title_short Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution
title_sort pilot study of a next-generation sequencing-based targeted anticancer therapy in refractory solid tumors at a korean institution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841558/
https://www.ncbi.nlm.nih.gov/pubmed/27105424
http://dx.doi.org/10.1371/journal.pone.0154133
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