Jean-Baptiste Bachet1, Fabien Gay, Raphaël Maréchal, Marie-Pierre Galais, Antoine Adenis, David Salako MsC, Jerome Cros, Pieter Demetter, Magali Svrcek, Armelle Bardier-Dupas, Jean-François Emile, Pascal Hammel, Christelle Ebenezer, Willy Berlier, Yann Godfrin, Thierry André. 1. From the *Department of Hepato-Gastroenterology, Pitié Salpêtrière Hospital, Paris; and †Erytech Pharma, Lyon, France; ‡Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium; §Department of Oncology, Centre François Baclesse, Caen; ∥Department of Oncology, Centre Oscar Lambret, Lille; and ¶Pathology Department, Beaujon Hospital, Paris, France; #Department of Pathology, Erasme Hospital, Brussels, Belgium; **Department of Pathology, Saint Antoine Hospital; and ††Department of Pathology, Pitié Salpêtrière Hospital, Paris; ‡‡Department of Pathology, Ambroise Paré Hospital, Boulogne-Billancourt; and §§Department of Gastroenterology, Beaujon Hospital; and Departments of ∥∥Medical Oncology and ¶¶Oncology, Saint-Antoine Hospital, Paris, France.
Abstract
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 ERY-ASP 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.
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 ERY-ASP 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.