The role of irinotecan-bevacizumab as rescue regimen in children with low-grade gliomas: a retrospective nationwide study in 72 patients
Abstract
Introduction : At least half of children with low-grade glioma (LGG) treated with first line chemotherapy experience a relapse/progression and may therefore need a second-line chemotherapy. Irinotecan-bevacizumab has been recommended in this setting in France after encouraging results of pilot studies. We performed a retrospective analysis to define the efficacy, toxicity and predictors for response to the combination on a larger cohort.
Methods : We reviewed the files from children < 19 years of age with progressive or refractory LGG treated between 2009 and 2016 in 7 French centers with this combination.
Results : 72 patients (median age 7.8 years [range 1–19]) received a median of 16 courses (range 3–30). The median duration of treatment was 9 months (range 1.4–16.2). 96% of patients experienced at least disease stabilization. The 6-month and 2-year progression-free survivals (PFS) were 91.7% [IC 95% 85.5–98.3] and 38.2% [IC 95% 28.2–51.8] respectively. No progression occurred after treatment in 18 patients with a median follow-up of 35.6 months (range 7.6–75.9 months). Younger patients had a worse PFS (p = 0.005). Prior chemoresistance, NF1 status, duration of treatment, histopathology or radiologic response did not predict response. The most frequent toxicities related to bevacizumab included grades 1–2 proteinuria in 21, epistaxis in 10, fatigue in 12 and hypertension in 8 while gastro-intestinal toxicity was the most frequent side effect related to irinotecan.
Conclusions : Bevacizumab-irinotecan has the potential of disease control clinically and radiographically in children with recurrent LGG whatever their previous characteristics; in many cases however these responses are not sustained, especially in younger children.