Pascal Hammel1, Portales Fabienne2, Laurent Mineur3, Jean-Philippe Metges4, Thierry Andre5, Christelle De La Fouchardiere6, Christophe Louvet7, Farid El Hajbi8, Roger Faroux9, Rosine Guimbaud10, David Tougeron11, Olivier Bouche12, Thierry Lecomte13, Christine Rebischung14, Christophe Tournigand15, Jerome Cros16, Richard Kay17, Adam Hamm18, Anu Gupta19, Jean-Baptiste Bachet20, Iman El Hariry19. 1. Digestive and Medical Oncology Unit, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, University Denis Diderot Paris VII, 92110 Clichy, France. Electronic address: pascal.hammel@aphp.fr. 2. Parc Euromedecine, 208 Rue Des Apothicaires, 34070 Montpellier, France. 3. Institut Sainte Catherine, Gastrointestinal and Liver Cancer Unit, Chemin de Baigne Pieds, 84000 Avignon, France. 4. CHRU de Brest - Hôpital Morvan, 2 Avenue Foch, 29609 Brest, France. 5. Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, and Sorbonne Universités, France. 6. Medical Oncology Department, Centre Leon Berard, Lyon, France. 7. Department of Medical Oncology, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014 Paris, France. 8. Centre Oscar Lambret, 3 Rue Frédéric Combemale, 59000 Lille, France. 9. Les Oudairies, Hospital La Roche-Sur-Yon, Boulevard Stephane Moreau, 85000 La Roche Sur Yon, France. 10. Institut Universitaire du Cancer, Avenue Hubert Curien, 31100 Toulouse, France. 11. Gastroenterology Department and Medical Oncology Department, Poitiers University Hospital, Faculty of Medicine of Poitiers, 86000 Poitiers, France. 12. Service Oncologie Digestive, CHU Reims, Avenue Général Koenig, 51092 Reims Cede, France. 13. Department of Hepatogastroenterology and Digestive Oncology, CHU de Tours, 37044 Tours Cedex, France. 14. Groupe Hospitalier Mutualiste de Grenoble, 8 Rue Docteur Calmette, 38100 Grenoble, France. 15. Service d'Oncologie médicale, Hôpital Henri Mondor, AP-HP, Université Paris-Est, 94010 Créteil, France. 16. Beaujon University Hospital, Department of Pathology-INSERM U1149, 100 Bvd Gal Lerclerc, 92110 Clichy, France. 17. RK Statistics Ltd, St Giles View, Main Street, Great Longstone, Bakewell, DE45 1TZ, UK. 18. Cytel Inc., 675 Massachusetts Ave Cambridge, MA 02139, USA. 19. ERYTECH, One Main Street, Suite 1150, Cambridge, MA 02142, USA. 20. Sorbonne Universités, UPMC Université, Gastroenterology and Digestive Oncology Department, Pitié Salpêtrière Hospital, 75013 Paris, France.
Abstract
PURPOSE: This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma. METHODS:Eligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression. Secondary endpoints included OS and PFS in the entire population. RESULTS:141 patients were randomized (eryaspase arm, n = 95; control arm, n = 46). Median OS and PFS in patients with low ASNS expression were 6.2 months (95% CI, 5.1-8.8) in the eryaspase arm versus 4.9 months (3.1-7.1) in the control arm (HR, 0.63; 95% CI, 0.39-1.01; P = 0.056) and 2.0 months (95% CI, 1.8-3.4) in the eryaspase arm versus 1.8 months (1.4-3.8) in the control arm (HR, 0.67; 95% CI, 0.40-1.12; P = 0.127), respectively. In the entire population, median OS and PFS for the eryaspase arm versus control were 6.0 months versus 4.4 months (HR, 0.60; P = 0.008) and 2.0 months versus 1.6 months (HR, 0.56; 95% CI, 0.37-0.84; P = 0.005), respectively. The combination of eryaspase and chemotherapy was well tolerated. The most frequent Grade 3/4 adverse events in the eryaspase arm (n = 93) were gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), and physical health deterioration (12 [12.9%]). CONCLUSION: Eryaspase in combination with chemotherapy is associated with improvements in OS and PFS, irrespective of ASNS expression in second-line advanced pancreatic adenocarcinoma. A Phase III trial is underway.
RCT Entities:
PURPOSE: This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma. METHODS: Eligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression. Secondary endpoints included OS and PFS in the entire population. RESULTS: 141 patients were randomized (eryaspase arm, n = 95; control arm, n = 46). Median OS and PFS in patients with low ASNS expression were 6.2 months (95% CI, 5.1-8.8) in the eryaspase arm versus 4.9 months (3.1-7.1) in the control arm (HR, 0.63; 95% CI, 0.39-1.01; P = 0.056) and 2.0 months (95% CI, 1.8-3.4) in the eryaspase arm versus 1.8 months (1.4-3.8) in the control arm (HR, 0.67; 95% CI, 0.40-1.12; P = 0.127), respectively. In the entire population, median OS and PFS for the eryaspase arm versus control were 6.0 months versus 4.4 months (HR, 0.60; P = 0.008) and 2.0 months versus 1.6 months (HR, 0.56; 95% CI, 0.37-0.84; P = 0.005), respectively. The combination of eryaspase and chemotherapy was well tolerated. The most frequent Grade 3/4 adverse events in the eryaspase arm (n = 93) were gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), and physical health deterioration (12 [12.9%]). CONCLUSION: Eryaspase in combination with chemotherapy is associated with improvements in OS and PFS, irrespective of ASNS expression in second-line advanced pancreatic adenocarcinoma. A Phase III trial is underway.
Authors: Alexis Eras; Danna Castillo; Margarita Suárez; Nelson Santiago Vispo; Fernando Albericio; Hortensia Rodriguez Journal: Front Chem Date: 2022-05-26 Impact factor: 5.545
Authors: Lucas M Bush; Connor P Healy; Shwan B Javdan; Jonathan C Emmons; Tara L Deans Journal: Trends Pharmacol Sci Date: 2020-12-17 Impact factor: 14.819