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The role of irinotecan-bevacizumab as rescue regimen in children with low-grade gliomas: a retrospective nationwide study in 72 patients

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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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

m:

Months

y:

Years

ChemoR:

Chemoresistant

ChemoS:

Chemosensitive

MR:

Minor response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

PA/PMA:

Pilocytic astrocytoma/pilomyxoid astrocytoma

GG:

Ganglioglioma

WT:

Wild type

UNDETM:

Undetermined

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Author notes

  1. Charles de Marcellus

    Present address: Pediatric Intensive Care Unit, Necker-Enfants Malades University Hospital Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France

Authors and Affiliations

  1. Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, University Paris-Saclay, Villejuif, France

    Charles de Marcellus, Aurélie Cuinet, Claudia Pasqualini, Thibaut Butel, Christelle Dufour, Dominique Valteau-Couanet & Jacques Grill

  2. Department of Neuropathology, GHU Psychiatrie et Neurosciences, site Sainte-Anne, Paris, France

    Arnault Tauziède-Espariat & Pascale Varlet

  3. Department of Ophthalmology, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Descarte, Paris, France

    Matthieu P. Robert

  4. Department of Pediatric Neurosurgery, Necker-Enfants Malades University Hospital, Assistance Publique- Hôpitaux de Paris, Paris, France

    Kevin Beccaria & Stéphanie Puget

  5. Paediatric Radiology Department, AP-HP, Hôpital Necker Enfants Malades, Université de Paris, 75015, Paris, France

    Nathalie Boddaert

  6. Université de Paris, Institut Imagine INSERM U1163, 75015, Paris, France

    Nathalie Boddaert

  7. APHM, CHU Timone, Department of Pathology and Neuropathology and Aix-Marseille Univ, CNRS, INP Inst Neurophysiopathol, Marseille, France

    Dominique Figarella-Branger

  8. Department of Pediatric Oncology, Angers University Hospital, Angers, France

    Emilie De Carli

  9. SIREDO Center (Pediatric, Adolescent and Young Adults Oncology), Institut Curie, University of Paris, Paris, France

    Franck Bourdeaut

  10. Pediatric Oncology Unit, Oscar Lambret Comprehensive Cancer Center, Lille, France

    Pierre Leblond

  11. Department of Pediatric Hematology, Nancy University Hospital, Vandoeuvre-les-Nancy, France

    Fanny Fouyssac

  12. Department of Pediatric Hematology and Oncology, Aix Marseille Universityy, Assistance Publique-Hôpitaux de Marseille, Marseille, France

    Nicolas Andre

  13. Department of Hematology-Oncology, Children University Hospital, Toulouse, France

    Anne I. Bertozzi

  14. CNRS Unit 8203, Gustave Roussy, University Paris-Saclay, Villejuif, France

    Jacques Grill

  15. Borelli Centre UMR 9010, CNRS-SSA-ENS Paris Saclay-Paris University, Paris, France

    Matthieu P. Robert

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  1. Charles de Marcellus
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Contributions

JG, ATE, PV and CdM designed and conceptualized the report, acquired and interpreted patient data, drafted the manuscript for intellectual content, reviewed and revised the manuscript. AC, CP, MPR, KB, SP, NB, DFB, EdC, FB, PL, FF, NA, AIB, TB, CD and DVC acquired and interpreted patient data, reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Charles de Marcellus.

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Conflict of interest

No funds, grants, or other support was received. The authors have no relevant financial or non-financial interests to disclose. Dr Grill has received grant support from Hoffmann La Roche for a study with bevacizumab in pediatric high-grade gliomas.

Ethical approval

Ethical approval was waived by the local Ethics Committee of Gustave Roussy (CCTIRS no 14.817) in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

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Informed consent was obtained from all individual participants included in the study.

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de Marcellus, C., Tauziède-Espariat, A., Cuinet, A. et al. The role of irinotecan-bevacizumab as rescue regimen in children with low-grade gliomas: a retrospective nationwide study in 72 patients. J Neurooncol 157, 355–364 (2022). https://doi.org/10.1007/s11060-022-03970-4

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