Dasatinib Beats Imatinib in Childhood Leukemia

By David Douglas

January 28, 2020

NEW YORK (Reuters Health) - The second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective in children with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) than the first-generation inhibitor imatinib mesylate, according to new research.

As Dr. Ching-Hon Pui told Reuters Health by email, "Dasatinib resulted in superior results as compared to imatinib in the treatment of childhood Philadelphia chromosome-positive acute lymphoblastic leukemia, and provided excellent control of central-nervous-system leukemia without the use of prophylactic cranial irradiation."

Dr. Pui of St. Jude Children's Research Hospital, in Memphis, Tennessee, and colleagues conducted an open-label clinical trial at 20 hospitals in China.

The Chinese Children's Cancer Group enrolled a total of 225 patients of whom 189 were randomized to daily treatment with dasatinib 80 mg/m2 or imatinib 300 mg/m2.

Enrollment was stopped "after an interim analysis demonstrated that dasatinib yields a superior outcome," the team writes in JAMA Oncology. This was based on event-free three-year survival.

After a median follow-up of 26.4 months and in intention-to-treat analysis, the four-year event-free survival rate in the dasatinib group (71.0%) was significantly greater than in the imatinib group (48.9%).

The rates of any relapse were 19.8% and 34.4%, respectively, and the cumulative risk of an isolated central-nervous-system relapse was 2.7% and 8.4%.

There were no significant differences in the frequency of severe toxic effects between groups.

The investigators also point out that "of the 40 patients who had completed ALL therapy in this study, thus far, 3 of 15 imatinib-treated patients as opposed to 2 of 25 dasatinib-treated patients had relapsed after the cessation of treatment, pointing to more enduring effects of the latter regimen."

Dr. Karen Rabin of Texas Children's Cancer Center, in Houston, author of an accompanying editorial, told Reuters Health by email, "This is an important study which demonstrates the effectiveness of targeted therapy for Philadelphia chromosome-positive ALL in children, including the ability to control central nervous system disease without the use of cranial irradiation."

However Dr. Rabin cautions in her editorial that "Longer follow-up and additional studies will be important to more fully evaluate the benefit of this regimen."

The study had no commercial funding. Dr Pui has reeceived compensation for chairing a data safety monitoring board for a clinical trial of Bristol-Myers Squibb on dasatinib.

SOURCE: https://bit.ly/2RmkwwQ and https://bit.ly/2TQsCzi JAMA Oncology, online January 16, 2020.