Intravenous pegylated (PEG) Escherichia coli (E coli) asparaginase was associated with similar toxicity and efficacy compared with intramuscular native E coli L-asparaginase in children with newly diagnosed acute lymphoblastic leukemia, according to the results of a phase III trial (DFCI 05-001).1 Andrew E. Place, MD, of Dana-Farber Cancer Institute, Boston, and colleagues reported these findings in The Lancet Oncology. Anxiety appeared to be reduced in patients receiving intravenous PEG-asparaginase.
In the open-label trial, 551 patients aged 1 to 18 years were enrolled from 11 consortium sites in the United States and Canada between April 2005 and February 2010. Among 526 patients achieving complete remission after induction therapy, 463 were randomized to intravenous PEG-asparaginase (15 doses of 2,500 IU/m² every 2 weeks; n = 232) or intramuscular native E coli L-asparaginase (30 doses of 25,000 IU/m² weekly; n = 231) beginning at week 7 after study entry. The primary endpoint was the overall frequency of asparaginase-related toxicities, defined as allergy, pancreatitis, and thrombotic or bleeding complications.
There was no significant difference between the intravenous PEG-asparaginase group and the intramuscular native L-asparaginase group in terms of overall frequency of asparaginase-related toxicities (28% vs 26%, P = .60) or with regard to allergy (15% vs 9%, P = .36), pancreatitis (12% vs 10%, P = .55), or thrombotic or bleeding complications (7% vs 10%, P = .26).
Median follow-up was 6.0 years. Five-year disease-free survival was 90% (95% confidence interval [CI] = 86%–94%) in the intravenous PEG-asparaginase group and 89% (95% CI = 85%–93%) in the intramuscular native L-asparaginase group (P = .58).
A total of 105 patients in the intravenous PEG-asparaginase group and 97 in the intramuscular native L-asparaginase group participated in an optional quality-of-life analysis using the PedsQL [Pediatric Quality-of-Life Inventory] 3.0 Cancer Module. Significantly more anxiety was reported by parents for treatment anxiety (P = .02) and procedural anxiety (P = .01) and by patients for procedural anxiety (P = .03) in the intramuscular native L-asparaginase group. No differences in other domains were observed.
The most common grade ≥ 3 adverse events were bacterial or fungal infections (20% vs 22%) and asparaginase-related allergic reactions (6% vs 3%).
“Intravenous PEG-asparaginase was not more toxic than, was similarly efficacious to, and was associated with decreased anxiety compared with intramuscular native E coli L-asparaginase, supporting its use as the front-line asparaginase preparation in children with newly diagnosed acute lymphoblastic leukemia.” ■
Disclosure: The study was funded by the National Cancer Institute and Enzon Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
1. Place AE, Stevenson KE, Vrooman LM, et al: Intravenous pegylated asparaginase versus intramuscular native Escherichia coli-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCA 05-001): A randomized, open-label phase 3 trial. Lancet Oncol 16:1677-1690, 2015.