Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial.

Autor:	Moreno L; Vall d'Hebron University Hospital, Barcelona, Spain., Weston R; University of Birmingham, Birmingham, United Kingdom., Owens C; Children's Hospital Ireland, Dublin, Ireland., Valteau-Couanet D; Institut Gustave Roussy, Paris, France., Gambart M; Hôpital des Enfants, Bordeaux, France., Castel V; Hospital Universitario La Fe, Valencia, Spain., Zwaan CM; Princess Maxima Center, Utrecht, the Netherlands., Nysom K; Rigshospitalet, Copenhagen, Denmark., Gerber N; Universitats-Kinderspital, Zurich, Switzerland., Castellano A; Bambino Gesù Children's Hospital, Rome, Italy., Laureys G; University Hospital Gent, Gent, Belgium., Ladenstein R; St Anna Kinderspital, Vienna, Austria., Rössler J; Inselspital, Universitätsspital Bern, Bern, Switzerland., Makin G; Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, United Kingdom., Murphy D; NHS Greater Glasgow and Clyde, Glasgow, United Kingdom., Morland B; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom., Vaidya S; The Royal Marsden NHS Foundation Trust & Institute for Cancer Research, London, United Kingdom., Thebaud E; Hôpital Mère-Enfant, Nantes, France., van Eijkelenburg N; Princess Maxima Center, Utrecht, the Netherlands., Tweddle DA; The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom., Barone G; Great Ormond Street Hospital, London, United Kingdom., Tandonnet J; Hôpital des Enfants, Hémato-Oncologie, Bordeaux, France., Corradini N; Centre Léon Bérard, Lyon, France., Chastagner P; Hôpital d'Enfants, Nancy, France., Paillard C; Hôpital de Hautepierre, Strasbourg, France., Bautista FJ; Princess Maxima Center, Utrecht, the Netherlands., Gallego Melcon S; Vall d'Hebron University Hospital, Barcelona, Spain., De Wilde B; University Hospital Gent, Gent, Belgium., Marshall L; The Royal Marsden NHS Foundation Trust & Institute for Cancer Research, London, United Kingdom., Gray J; University Hospital Southampton, Southampton, United Kingdom., Burchill SA; St James University Hospital, Leeds, United Kingdom., Schleiermacher G; Institute Curie, Paris, France., Chesler L; The Royal Marsden NHS Foundation Trust & Institute for Cancer Research, London, United Kingdom., Peet A; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom., Leach MO; The Royal Marsden NHS Foundation Trust & Institute for Cancer Research, London, United Kingdom., McHugh K; Great Ormond Street Hospital, London, United Kingdom., Hayes R; Children's Hospital Ireland, Dublin, Ireland., Jerome N; The Royal Marsden NHS Foundation Trust & Institute for Cancer Research, London, United Kingdom., Caron H; Roche, Basel, Switzerland., Laidler J; University of Birmingham, Birmingham, United Kingdom., Fenwick N; University of Birmingham, Birmingham, United Kingdom., Holt G; University of Birmingham, Birmingham, United Kingdom., Moroz V; University of Birmingham, Birmingham, United Kingdom., Kearns P; University of Birmingham, Birmingham, United Kingdom., Gates S; University of Birmingham, Birmingham, United Kingdom., Pearson ADJ; The Royal Marsden NHS Foundation Trust & Institute for Cancer Research, London, United Kingdom., Wheatley K; University of Birmingham, Birmingham, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Apr 01; Vol. 42 (10), pp. 1135-1145. Date of Electronic Publication: 2024 Jan 08.
DOI:	10.1200/JCO.23.00458
Abstrakt:	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.
Databáze:	MEDLINE
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