Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial.

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.

• Authors: Pascal Hammel, Portales Fabienne, Laurent Mineur, Jean-Philippe Metges, Thierry Andre, Christelle De La Fouchardiere, Christophe Louvet, Farid El Hajbi, Roger Faroux, Rosine Guimbaud, David Tougeron, Olivier Bouche, Thierry Lecomte, Christine Rebischung, Christophe Tournigand, Jerome Cros, Richard Kay, Adam Hamm, Anu Gupta, Jean-Baptiste Bachet, Iman El Hariry
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 124 Pg. 91-101 (01 2020) ISSN: 1879-0852 [Electronic] England
• PMID: 31760314 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Organoplatinum Compounds
• Deoxycytidine
• Asparaginase
• eryaspase
• Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor
• ASNS protein, human
• Leucovorin
• Fluorouracil
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Asparaginase (administration & dosage, adverse effects)
• Biopsy
• Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor (metabolism)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoplasm Staging
• Neutropenia (chemically induced, epidemiology)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Pancreas (pathology)
• Pancreatic Neoplasms (drug therapy, mortality, pathology)
• Progression-Free Survival
• Response Evaluation Criteria in Solid Tumors
• Gemcitabine