Moreno, Lucas; Weston, Rebekah; Owens, Cormac; Valteau-Couanet, Dominique; Gambart, Marion; Castel, Victoria; Zwaan, C Michel; Nysom, Karsten; Gerber, Nicolas; Castellano, Aurora; Laureys, Genevieve; Ladenstein, Ruth; Rössler, Jochen; Makin, Guy; Murphy, Dermot; Morland, Bruce; Vaidya, Sucheta; Thebaud, Estelle; van Eijkelenburg, Natasha; Tweddle, Deborah A; ... (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 : official journal of the American Society of Clinical Oncology, 42(10), pp. 1135-1145. American Society of Clinical Oncology 10.1200/JCO.23.00458
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Haematology/Oncology |
UniBE Contributor: |
Rössler, Jochen Karl |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1527-7755 |
Publisher: |
American Society of Clinical Oncology |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
09 Jan 2024 10:30 |
Last Modified: |
29 Mar 2024 00:13 |
Publisher DOI: |
10.1200/JCO.23.00458 |
PubMed ID: |
38190578 |
BORIS DOI: |
10.48350/191348 |
URI: |
https://boris.unibe.ch/id/eprint/191348 |