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

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.
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https://hal.sorbonne-universite.fr/hal-03198137
Contributeur : Gestionnaire Hal-Su <>
Soumis le : mercredi 14 avril 2021 - 15:34:28
Dernière modification le : samedi 17 avril 2021 - 03:30:31

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Thomas Aparicio, Nathalie Cozic, Christelle de la Fouchardière, Emeline Meriaux, Jérome Plaza, et al.. The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program. Targeted Oncology, Springer Verlag (Germany), 2021, ⟨10.1007/s11523-021-00811-8⟩. ⟨hal-03198137⟩

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