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

Translational Oncology

Clémentine Peyramaure¹  David Pérol²  Olivier Trédan³  Jean-Yves Blay⁴  Isabelle Ray-Coquard⁴  Philippe A. Cassier⁴  Christelle de la Fouchardière⁴  Mathieu Sarabi⁴  Pierre Guibert⁴  Clélia Coutzac⁴  Michel Rivoire⁴  Pauline Rochefort⁴  Nathalie Marques⁴  Catherine Terret⁵  Patrice Peyrat⁵  Aurélien Dupré⁵  Lauriane Eberst⁶  Françoise Desseigne⁶  Camille Pacaud⁷  Sandrine Boyault⁸  Valery Attignon⁹ 

[1] Corresponding author.;Université Claude Bernard Lyon I, Lyon, France;Direction de la Recherche Clinique et de l'Innovation, Centre Léon Bérard, Lyon, France;Département de Cancérologie Médicale, Centre Léon Bérard, 28 rue Laennec, Lyon 69008, France;Département de Chirurgie, Centre Léon Bérard, Lyon, France;Département de la Recherche Translationelle et de l'Innovation, Centre Léon Bérard, Lyon, France;Institut de Cancérologie de Strasbourg, Strasbourg, France;Service d'Onco-Hémato Pédiatrie, Hôpital Hautepierre, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France;Service d'Oncologie, Centre Hospitalier Universitaire de Limoges, Limoges, France;

关键词: Oesophageal cancer;    Gastric cancer;    Molecular alterations, molecular-targeted agents;    NGS;    CGH;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown