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Asparagine synthetase expression and phase i study with l-asparaginase encapsulated in red blood cells in patients with pancreatic adenocarcinoma

par Bachet, Jean-Baptiste;Bardier-Dupas, Armelle;Emile, Jean-François;Hammel, Pascal;Ebenezer, Christelle;Berlier, Willy;Godfrin, Yann;André, Thierry;Gay, Fabien;Marechal, Raphaël ;Galais, Marie Pierre;Adenis, Antoine;Salako, David;Cros, Jérôme;Demetter, Pieter ;Svrcek, Magali
Référence Pancreas, 44, 7, page (1141-1147)
Publication Publié, 2015-10

Article révisé par les pairs

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Résumé :

Objectives: Asparaginase encapsulated in erythrocytes (ERY-ASP) is a potentially effective drug in patients with pancreatic adenocarcinoma (PAC) with null/low asparagine synthetase (ASNS) expression. Our aims were to assess ASNS expression in PAC from a large cohort and its prognostic and/or predictive value and to conduct a phase I trial with ERYASP in patients with metastatic PAC. Methods: Asparagine synthetase expression was evaluated using immunohistochemistry in resected PAC (471 patients) and in pairs of primary tumor and metastases (55 patients). Twelve patients were included in the phase I trial and received a single administration of ERY-ASP (25-150 IU/kg). Results: Null/low ASNS expression was found in 79.4% of the resected PAC with a high concordance between primary tumor and metastases. Asparagine synthetase expression was significantly correlated with sex and CXCR4 expression. In the phase I trial, ERY-ASP was well tolerated by patients with metastatic PAC. No patient had DLTs, and 6 patients had at least 1 ERY-ASP causally related adverse event out of the 12 adverse events reported. Conclusions: Given the high rate of PAC with null/low ASNS expression and the good tolerability profile of ERY-ASP, ERY-ASP should be evaluated in further clinical studies in metastatic PAC.