Cassier Philippe A, Peyramaure Clémentine, Attignon Valery, Eberst Lauriane, Pacaud Camille, Boyault Sandrine, Desseigne Françoise, Sarabi Mathieu, Guibert Pierre, Rochefort Pauline, Marques Nathalie, Rivoire Michel, Dupré Aurélien, Peyrat Patrice, Terret Catherine, Ray-Coquard Isabelle, Coutzac Clélia, Pérol David, Blay Jean-Yves, Trédan Olivier, de la Fouchardière Christelle
Département de Cancérologie Médicale, Centre Léon Bérard, 28 rue Laennec, Lyon 69008, France.
Service d'Oncologie, Centre Hospitalier Universitaire de Limoges, Limoges, France.
Transl Oncol. 2022 Jan;15(1):101266. doi: 10.1016/j.tranon.2021.101266. Epub 2021 Nov 15.
Chemotherapy, anti-HER2 and PD-1 antibodies are standard treatments but only a minority of patients derive long-term benefit from these agents.
In this report we describe the mutational landscape and outcome of patients with gastroesophageal cancers enroled in the ProfiLER program.
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.
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.
化疗、抗HER2和PD-1抗体是标准治疗方法，但只有少数患者能从这些药物中获得长期益处。
在本报告中，我们描述了参与ProfiLER项目的食管癌和胃癌患者的突变图谱及预后情况。
147例患者中，腺癌（n = 86，59%）、印戒细胞癌（n = 37，25%）和鳞状细胞癌（n = 21，14%）是主要的组织学类型。114例（78%）患者可进行基因组分析。最常见的基因组改变包括ERBB2（15%）、KRAS（12%）、CCND1（7%）、FGFR1 - 3（8%）、EGFR（5%）和MET（3%）、TP53（51%）以及CDKN2A/B（10%）。ERBB2、MET和FGFR改变仅在腺癌和印戒细胞癌亚型中发现，而CCND1扩增、TP53突变和CDKN2A/B缺失在腺癌和鳞状细胞癌亚型中均有发现。9例（8%）患者接受了与其基因组改变相匹配的治疗，其中5例实现了疾病控制。在一项探索性分析中，诊断时为IV期疾病且有可操作改变的患者与无此改变的患者相比，总生存期更长。
对晚期食管癌和胃癌患者进行基因组分析可在很大比例的患者中识别出可操作的改变。增加分子匹配治疗的可及性可能改善该疾病患者的生存率。
