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

Thomas Aparicio (1) , Nathalie Cozic (2, 3, 4) , Christelle de La Fouchardière (5, 6) , Emeline Meriaux (7, 8) , Jérome Plaza , Laurent Mineur , Rosine Guimbaud (9) , Emmanuelle Samalin (10) , Florence Mary (11) , Thierry Lecomte (12) , Carlos Gomez-Roca (13, 14) , Paul-Arthur Haineaux (15) , Alain Gratet (16) , Jannick Selves (14) , Yves Menu (17) , Nikias Colignon (17) , Laetitia Johnson (18) , Frédéric Legrand (19) , Gilles Vassal (2, 20, 21)

1 AP-HP - Hopital Saint-Louis [AP-HP]
2 IGR - Institut Gustave Roussy
3 SBE - Service de biostatistique et d'épidémiologie
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 Centre Léon Bérard [Lyon]
6 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
7 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
8 CRLCC René Gauducheau
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 ICM - Institut régional de Cancérologie de Montpellier
11 Hôpital Avicenne [AP-HP]
12 N2Cox - Niche, Nutrition, Cancer et métabolisme oxydatif
13 Institut Claudius Regaud
14 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
15 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
16 Clinique Pasteur [Toulouse]
17 CHU Saint-Antoine [AP-HP]
18 UNICANCER
19 INCa - Institut national du cancer
20 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
21 Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy]

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.

Domaines: Sciences du Vivant [q-bio]

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, 2021, ⟨10.1007/s11523-021-00811-8⟩. ⟨hal-03198137⟩