Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial ( ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m2per day for 6 weeks; 4-week treatment break; then up to 12 × 28-day cycles of TMZ [cycle 1: 150 mg/m2per day, days 1 to 5; cycles 2 to 12: 200 mg/m2per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee-assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.

Phase II, open-label, randomized, multicenter trial (HERBY) of Bevacizumab in pediatric patients with newly diagnosed high-grade glioma / Grill, Jacques; Massimino, Maura; Bouffet, Eric; Azizi, Amedeo A; Mccowage, Geoffrey; Cañete, Adela; Saran, Frank; Le Deley, Marie-Cécile; Varlet, Pascale; Morgan, Paul S; Jaspan, Tim; Jones, Chris; Giangaspero, Felice; Smith, Helen; Garcia, Josep; Elze, Markus C; Rousseau, Raphaël F; Abrey, Lauren; Hargrave, Darren; Vassal, Gilles. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - 36:10(2018), pp. 951-958. [10.1200/JCO.2017.76.0611]

Phase II, open-label, randomized, multicenter trial (HERBY) of Bevacizumab in pediatric patients with newly diagnosed high-grade glioma

Giangaspero, Felice;
2018

Abstract

Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial ( ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m2per day for 6 weeks; 4-week treatment break; then up to 12 × 28-day cycles of TMZ [cycle 1: 150 mg/m2per day, days 1 to 5; cycles 2 to 12: 200 mg/m2per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee-assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.
2018
Bevacizumab (BEV); glioblastoma; radiotherapy plus temozolomide (RT+TMZ); pediatric patients; HERBY trial
01 Pubblicazione su rivista::01a Articolo in rivista
Phase II, open-label, randomized, multicenter trial (HERBY) of Bevacizumab in pediatric patients with newly diagnosed high-grade glioma / Grill, Jacques; Massimino, Maura; Bouffet, Eric; Azizi, Amedeo A; Mccowage, Geoffrey; Cañete, Adela; Saran, Frank; Le Deley, Marie-Cécile; Varlet, Pascale; Morgan, Paul S; Jaspan, Tim; Jones, Chris; Giangaspero, Felice; Smith, Helen; Garcia, Josep; Elze, Markus C; Rousseau, Raphaël F; Abrey, Lauren; Hargrave, Darren; Vassal, Gilles. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - 36:10(2018), pp. 951-958. [10.1200/JCO.2017.76.0611]
File allegati a questo prodotto
File Dimensione Formato  
Grill_Phase II_2018.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 949.08 kB
Formato Adobe PDF
949.08 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1081054
Citazioni
  • ???jsp.display-item.citation.pmc??? 41
  • Scopus 84
  • ???jsp.display-item.citation.isi??? 83
social impact