In a Children’s Oncology Group phase II trial reported in the Journal of Clinical Oncology, Katherine E. Warren, MD, and colleagues found that lenalidomide showed activity in children with pilocytic astrocytomas and optic pathway gliomas who did not respond to initial therapy.
As noted by the investigators, “Phase I studies [in low-grade gliomas] indicated greater tolerability of lenalidomide in children compared with adults and a potential dose-response effect.”
Katherine E. Warren, MD
Study Details
In the multicenter trial, 74 eligible patients were randomly assigned between March 2012 and January 2017 to receive low-dose lenalidomide at 20 mg/m2 (n = 37) or high-dose lenalidomide at 115 mg/m2 (n = 37) once daily for 21 days in 28-day cycles. The primary objective was to determine the objective response rate and rate of early disease progression on central review in the two groups. If 3 or fewer patients had an objective response or at least 15 of 37 patients experienced early disease progression in any group, it was considered that there was insufficient evidence for further evaluation of the dose tested.
Key Findings
The predefined activity level of interest was achieved in both groups. Objective response was observed in four patients in the low-dose group and four in the high-dose group (12.9%, 95% confidence interval [CI] = 4.09%–22.6%, in both groups). Early disease progression (range = 1.7–5.5 months) occurred in 10 patients overall, including 6 in the low-dose group and 4 in the high-dose group. Estimated probability of early progression was 16.2% (95% CI = 9.2%–29.5%) in the low-dose group and 10.8% (95% CI = 5.5%–23.1%) in the high-dose group.
A total of 12 patients in the low-dose group vs 6 in the high-dose group completed 26 cycles of treatment. Median number of cycles was 14 (range = 2–26) vs 11 (range = 1–26).
Event-free survival and overall survival at 2 years were 43% (95% CI = 27%–58%) and 95% (95% CI = 80%–99%) in the low-dose group, respectively, and 48% (95% CI = 31%–63%) and 92% (95% CI = 77%–97%) in the high-dose group.
Adverse events led to dose reduction in 5 patients (14%) in the low-dose group vs 24 (65%) in the high-dose group; adverse events led to discontinuation of treatment in 2 patients (5%) vs 14 patients (38%). Grade 3 or 4 adverse events occurred in 43% vs 84% of patients, most commonly decreased neutrophils in both groups (30% vs 70%).
The investigators concluded, “Lenalidomide demonstrates a sufficient level of activity in children with low-grade glioma to warrant further exploration. Low-dose (20 mg/m2/dose administered once daily [for] 21 days of each 28-day cycle) lenalidomide appears to have better tolerability with comparable activity.”
Dr. Warren, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Children’s Oncology Group, National Cancer Institute, St. Baldrick’s Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
