Bevacizumab, irinotecan, or topotecan added to temozolomide for children with relapsed and refractory neuroblastoma: results of the ITCC-SIOPEN BEACON-Neuroblastoma trial
Bevacizumab, irinotecan, or topotecan added to temozolomide for children with relapsed and refractory neuroblastoma: results of the ITCC-SIOPEN BEACON-Neuroblastoma trial
PURPOSE: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). MATERIALS AND METHODS: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. RESULTS: One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). CONCLUSION: The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era.
1135-1145
Moreno, Lucas
132a48b4-e7a1-4faf-8471-ba5e0d26e9d0
Weston, Rebekah
556b4436-c777-4cca-9303-d84fc372fe71
Owens, Cormac
9ef9d116-2e58-49be-92ce-8f0311d63bc1
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
on behalf of Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN)
1 April 2024
Moreno, Lucas
132a48b4-e7a1-4faf-8471-ba5e0d26e9d0
Weston, Rebekah
556b4436-c777-4cca-9303-d84fc372fe71
Owens, Cormac
9ef9d116-2e58-49be-92ce-8f0311d63bc1
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
Moreno, Lucas, Weston, Rebekah and Owens, Cormac
,
et al. and on behalf of Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN)
(2024)
Bevacizumab, irinotecan, or topotecan added to temozolomide for children with relapsed and refractory neuroblastoma: results of the ITCC-SIOPEN BEACON-Neuroblastoma trial.
Journal of Clinical Oncology, 42 (10), .
(doi:10.1200/JCO.23.00458).
Abstract
PURPOSE: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). MATERIALS AND METHODS: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. RESULTS: One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). CONCLUSION: The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era.
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Accepted/In Press date: 5 October 2023
Published date: 1 April 2024
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Local EPrints ID: 485710
URI: http://eprints.soton.ac.uk/id/eprint/485710
ISSN: 1527-7755
PURE UUID: 81d2ce56-ab74-4ced-bdbc-3d2e7712abfd
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Date deposited: 15 Dec 2023 17:32
Last modified: 13 Apr 2024 01:38
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Author:
Lucas Moreno
Author:
Rebekah Weston
Author:
Cormac Owens
Corporate Author: et al.
Corporate Author: on behalf of Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN)
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