In a Chinese phase III trial reported in JAMA Oncology, Shen et al found that dasatinib was associated was superior event-free survival vs imatinib when combined with intensive chemotherapy in pediatric patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) not receiving prophylactic cranial irradiation.
Study Details
In the multicenter trial, which enrolled patients between January 2015 and September 2018, 186 patients aged 0 to 18 years were randomly assigned to receive dasatinib at 80 mg/m2 per day (n = 92) or imatinib at 300 mg/m2 per day (n = 97). All patients received induction therapy with prednisone, vincristine, daunorubicin, and pegaspargase, followed by cyclophosphamide, cytarabine, and mercaptopurine. Consolidation treatment consisted of high-dose methotrexate, mercaptopurine, and triple intrathecal therapy. None of the patients was given prophylactic cranial irradiation.
Patients had a median age of 7.8 years. The primary endpoint was event-free survival on intention-to-treat analysis.
KEY POINTS
- Dasatinib was associated with improved event-free and overall survival vs imatinib.
- Event-free survival at 4 years was 71.0% vs 48.9%.
Event-Free Survival
The trial met criteria for randomization to be stopped early, and imatinib was replaced with dasatinib in all patients still receiving treatment. Event-free survival at 4 years was 71.0% in the dasatinib group vs 48.9% in the imatinib group (P = .005). Overall survival at 4 years was 88.4% vs 69.2% (P = .04).
The 4-year cumulative risk of any relapse was 19.8% vs 34.4% (P = .01). The 4-year cumulative risk of an isolated central nervous system relapse was 2.7% vs 8.4% (P = .06).
Toxicity
The investigators stated that there were no significant differences in the frequency of severe toxic effects between the two treatment groups. Infections and pancreatitis were the most common adverse events, with five fatal infections occurring in each group. No deaths were attributed directly to dasatinib or imatinib treatment.
The investigators concluded, “Intensive chemotherapy, including dasatinib at a dosage of 80mg/m2 per day, yielded superior results in the treatment of Philadelphia chromosome–positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation.”
Ching-Hon Pui, MD, of the Department of Oncology, St. Jude Children’s Research Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by a grant from the U.S. National Cancer Institute, grants from the National Natural Science Foundation of China, St. Baldrick’s Foundation, China National Children’s Medical Center (Shanghai), and others. For full disclosures of the study authors, visit jamanetwork.com.
