克唑替尼治疗化疗耐药 MET 扩增食管胃腺癌的活性：来自 AcSé-Crizotinib 项目的结果。

The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program.

机构信息

Gastroenterology and Digestive Oncology Department, Hôpital Saint Louis, APHP, Université de Paris, 1 Avenue Claude Vellefaux, 75010, Paris, France.

Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France.

出版信息

Target Oncol. 2021 May;16(3):381-388. doi: 10.1007/s11523-021-00811-8. Epub 2021 Apr 13.

DOI:10.1007/s11523-021-00811-8

PMID:33847874

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8105218/

Abstract

BACKGROUND

The AcSé-crizotinib program provides extensive screening of crizotinib-targeted genomic alteration in several malignancies. We here report the results in patients with esogastric MET-amplified adenocarcinomas.

OBJECTIVE

The objective of the study was to evaluate the efficacy and tolerability of crizotinib in patients with pretreated esogastric MET-amplified adenocarcinoma who have no alternative treatment options.

PATIENTS AND METHODS

MET expression was evaluated by fluorescence in situ hybridization in tumor samples with immunohistochemistry scores ≥ 2+. Patients with chemo-refractory tumors showing ≥ 6 MET copies were eligible for crizotinib 250 mg twice daily. The primary efficacy outcome was the objective response rate after two cycles of crizotinib.

RESULTS

MET was prospectively analyzed in 570 esogastric adenocarcinomas. Amplifications were found in 35/570 adenocarcinomas (29/523 gastric and 6/47 esophageal). Nine patients were treated with crizotinib. The objective response rate after two cycles was 33.3% (95% CI 7.5-70), the best overall response rate was 55.6% (95% CI 21.2-86.3), with median progression-free survival of 3.2 months (95% CI 1.0-5.4), and overall survival of 8.1 months (95% CI 1.7-24.6). Safety was consistent with that previously reported for crizotinib.

CONCLUSIONS

Large-scale screening for MET-amplified esogastric adenocarcinomas is feasible. MET amplification was observed in 5.5% of gastric and 12.8% of esophageal adenocarcinomas. Crizotinib shows encouraging results in selected patients. Thus, c-MET inhibition for MET-amplified tumors deserves further evaluation.

TRIAL REGISTRATION NUMBER

NCT02034981.

DATE OF REGISTRATION

14 January 2014.

摘要

背景

AcSé-crizotinib 项目对多种恶性肿瘤进行了广泛的克唑替尼靶向基因组改变筛选。我们在此报告了胃食管 MET 扩增腺癌患者的结果。

目的

本研究的目的是评估克唑替尼在预处理过的胃食管 MET 扩增腺癌患者中的疗效和耐受性，这些患者没有其他治疗选择。

患者和方法

采用免疫组织化学评分≥2+的肿瘤样本进行荧光原位杂交检测 MET 表达。对化疗耐药的肿瘤，若 MET 拷贝数≥6，则有资格接受克唑替尼 250mg 每日两次治疗。主要疗效终点是克唑替尼两个周期后的客观缓解率。

结果

前瞻性分析了 570 例胃食管腺癌患者的 MET。在 570 例腺癌中发现了 35 例扩增（523 例胃腺癌中有 29 例，47 例食管腺癌中有 6 例）。9 例患者接受了克唑替尼治疗。两个周期后的客观缓解率为 33.3%（95%CI7.5-70），最佳总缓解率为 55.6%（95%CI21.2-86.3），中位无进展生存期为 3.2 个月（95%CI1.0-5.4），总生存期为 8.1 个月（95%CI1.7-24.6）。安全性与克唑替尼先前报道的一致。