Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program

Background: Chemotherapy, anti-HER2 and PD-1 antibodies are standard treatments but only a minority of patients derive long-term benefit from these agents. Methods: In this report we describe the mutational landscape and outcome of patients with gastroesophageal cancers enroled in the ProfiLER progr...

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Autores principales:	Philippe A. Cassier, Clémentine Peyramaure, Valery Attignon, Lauriane Eberst, Camille Pacaud, Sandrine Boyault, Françoise Desseigne, Mathieu Sarabi, Pierre Guibert, Pauline Rochefort, Nathalie Marques, Michel Rivoire, Aurélien Dupré, Patrice Peyrat, Catherine Terret, Isabelle Ray-Coquard, Clélia Coutzac, David Pérol, Jean-Yves Blay, Olivier Trédan, Christelle de la Fouchardière
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Oesophageal cancer Gastric cancer Molecular alterations, molecular-targeted agents NGS CGH Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/af51f8a698dc4ce7a25e81ac463e3700
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spelling	oai:doaj.org-article:af51f8a698dc4ce7a25e81ac463e37002021-11-16T04:09:32ZPrecision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program1936-523310.1016/j.tranon.2021.101266https://doaj.org/article/af51f8a698dc4ce7a25e81ac463e37002022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1936523321002576https://doaj.org/toc/1936-5233Background: Chemotherapy, anti-HER2 and PD-1 antibodies are standard treatments but only a minority of patients derive long-term benefit from these agents. Methods: In this report we describe the mutational landscape and outcome of patients with gastroesophageal cancers enroled in the ProfiLER program. Results: Adenocarcinoma (n = 86, 59%), signet-cell (n = 37, 25%) and squamous-cell (n = 21, 14%) were the dominant histology amongst 147 patients. Genomic analyses could be performed for 114 (78%) patients. The most common genomic alterations involved ERBB2 (15%), KRAS (12%), CCND1 (7%), FGFR1–3 (8%), EGFR (5%) and MET (3%), TP53 (51%) and CDKN2A/B (10%). ERBB2, MET and FGFR alterations were found exclusively in the adenocarcinoma and signet-cell subtypes, while CCND1 amplification, TP53 mutations and CDKN2A/B loss were found in both adenocarcinoma and squamous-cell subtypes. Nine patients (8%) received therapy matched to their genomic alteration, with 5 of them achieving disease control. In an exploratory analysis, patients with stage IV disease at diagnosis who had an actionable alteration had longer overall survival compared to those without. Conclusion: Genomic profiling for patients with advanced gastroesophageal cancers allows the identification of actionable alterations in large proportion of patients. Increased accessibility to molecularly matched therapy may improve survival in this disease.Philippe A. CassierClémentine PeyramaureValery AttignonLauriane EberstCamille PacaudSandrine BoyaultFrançoise DesseigneMathieu SarabiPierre GuibertPauline RochefortNathalie MarquesMichel RivoireAurélien DupréPatrice PeyratCatherine TerretIsabelle Ray-CoquardClélia CoutzacDavid PérolJean-Yves BlayOlivier TrédanChristelle de la FouchardièreElsevierarticleOesophageal cancerGastric cancerMolecular alterations, molecular-targeted agentsNGSCGHNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTranslational Oncology, Vol 15, Iss 1, Pp 101266- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Oesophageal cancer Gastric cancer Molecular alterations, molecular-targeted agents NGS CGH Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Oesophageal cancer Gastric cancer Molecular alterations, molecular-targeted agents NGS CGH Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Philippe A. Cassier Clémentine Peyramaure Valery Attignon Lauriane Eberst Camille Pacaud Sandrine Boyault Françoise Desseigne Mathieu Sarabi Pierre Guibert Pauline Rochefort Nathalie Marques Michel Rivoire Aurélien Dupré Patrice Peyrat Catherine Terret Isabelle Ray-Coquard Clélia Coutzac David Pérol Jean-Yves Blay Olivier Trédan Christelle de la Fouchardière Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program
description	Background: Chemotherapy, anti-HER2 and PD-1 antibodies are standard treatments but only a minority of patients derive long-term benefit from these agents. Methods: In this report we describe the mutational landscape and outcome of patients with gastroesophageal cancers enroled in the ProfiLER program. Results: Adenocarcinoma (n = 86, 59%), signet-cell (n = 37, 25%) and squamous-cell (n = 21, 14%) were the dominant histology amongst 147 patients. Genomic analyses could be performed for 114 (78%) patients. The most common genomic alterations involved ERBB2 (15%), KRAS (12%), CCND1 (7%), FGFR1–3 (8%), EGFR (5%) and MET (3%), TP53 (51%) and CDKN2A/B (10%). ERBB2, MET and FGFR alterations were found exclusively in the adenocarcinoma and signet-cell subtypes, while CCND1 amplification, TP53 mutations and CDKN2A/B loss were found in both adenocarcinoma and squamous-cell subtypes. Nine patients (8%) received therapy matched to their genomic alteration, with 5 of them achieving disease control. In an exploratory analysis, patients with stage IV disease at diagnosis who had an actionable alteration had longer overall survival compared to those without. Conclusion: Genomic profiling for patients with advanced gastroesophageal cancers allows the identification of actionable alterations in large proportion of patients. Increased accessibility to molecularly matched therapy may improve survival in this disease.
format	article
author	Philippe A. Cassier Clémentine Peyramaure Valery Attignon Lauriane Eberst Camille Pacaud Sandrine Boyault Françoise Desseigne Mathieu Sarabi Pierre Guibert Pauline Rochefort Nathalie Marques Michel Rivoire Aurélien Dupré Patrice Peyrat Catherine Terret Isabelle Ray-Coquard Clélia Coutzac David Pérol Jean-Yves Blay Olivier Trédan Christelle de la Fouchardière
author_facet	Philippe A. Cassier Clémentine Peyramaure Valery Attignon Lauriane Eberst Camille Pacaud Sandrine Boyault Françoise Desseigne Mathieu Sarabi Pierre Guibert Pauline Rochefort Nathalie Marques Michel Rivoire Aurélien Dupré Patrice Peyrat Catherine Terret Isabelle Ray-Coquard Clélia Coutzac David Pérol Jean-Yves Blay Olivier Trédan Christelle de la Fouchardière
author_sort	Philippe A. Cassier
title	Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program
title_short	Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program
title_full	Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program
title_fullStr	Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program
title_full_unstemmed	Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program
title_sort	precision medicine for patients with gastro-oesophageal cancer: a subset analysis of the profiler program
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/af51f8a698dc4ce7a25e81ac463e3700
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Precision medicine for patients with gastro-oesophageal cancer: A subset analysis of the ProfiLER program

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