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. Conclusion. Bevacizumab-irinotecan is highly effective for children with recurrent LGG who have failed standard chemotherapy regimens whatever their clinical characteristics, only younger children had a worse PFS.