TY - JOUR
T1 - Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma
T2 - Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial
AU - Moreno, Lucas
AU - Weston, Rebekah
AU - Owens, Cormac
AU - Valteau-Couanet, Dominique
AU - Gambart, Marion
AU - Castel, Victoria
AU - Zwaan, C Michel
AU - Nysom, Karsten
AU - Gerber, Nicolas
AU - Castellano, Aurora
AU - Laureys, Genevieve
AU - Ladenstein, Ruth
AU - Rössler, Jochen
AU - Makin, Guy
AU - Murphy, Dermot
AU - Morland, Bruce
AU - Vaidya, Sucheta
AU - Thebaud, Estelle
AU - van Eijkelenburg, Natasha
AU - Tweddle, Deborah A
AU - Barone, Giuseppe
AU - Tandonnet, Julie
AU - Corradini, Nadege
AU - Chastagner, Pascal
AU - Paillard, Catherine
AU - Bautista, Francisco J
AU - Gallego Melcon, Soledad
AU - De Wilde, Bram
AU - Marshall, Lynley
AU - Gray, Juliet
AU - Burchill, Susan A
AU - Schleiermacher, Gudrun
AU - Chesler, Louis
AU - Peet, Andrew
AU - Leach, Martin O
AU - McHugh, Kieran
AU - Hayes, Roisin
AU - Jerome, Neil
AU - Caron, Hubert
AU - Laidler, Jennifer
AU - Fenwick, Nicola
AU - Holt, Grace
AU - Moroz, Veronica
AU - Kearns, Pamela
AU - Gates, Simon
AU - Pearson, Andrew D J
AU - Wheatley, Keith
AU - Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN)
PY - 2024/4/1
Y1 - 2024/4/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Bevacizumab/adverse effects
KW - Child
KW - Child, Preschool
KW - Dacarbazine/adverse effects
KW - Humans
KW - Infant
KW - Irinotecan/therapeutic use
KW - Neoplasm Recurrence, Local/drug therapy
KW - Neuroblastoma/pathology
KW - Temozolomide/therapeutic use
KW - Topotecan/adverse effects
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85186742717&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.00458
DO - 10.1200/JCO.23.00458
M3 - Journal article
C2 - 38190578
SN - 0732-183X
VL - 42
SP - 1135
EP - 1145
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 10
ER -