Randomized comparisons of bevacizumab(B) and irinotecan(I),added to temozolomide(T), in children with relapsed/refractory high-risk neuroblastoma(RR-HRNB); survival results of the ITCC-SIOPEN beacon-neuroblastoma phase 2 trial
Wheatley, K. Holt, G. Owens, C. Valteau-Couanet, D. Gambart, M. Castel, V. Van Eijkelenburg, N. Castellano, A. Nysom, K. Gerber, N.
Wheatley, K.
Holt, G.
Owens, C.
Valteau-Couanet, D.
Gambart, M.
Castel, V.
Van Eijkelenburg, N.
Castellano, A.
Nysom, K.
Gerber, N.
Citations
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Abstract
Background and Aims: BEACON is a randomized phase 2 trial
assessing whether bevacizumab adds to chemotherapy and evaluating
chemotherapy regimens for RR-HRNB.
Methods: Patients with RR-HRNB underwent randomizations, in a
3x2 factorial design, to: T, IT or topotecan (To)-T, +/- B. Toxicity and
response were already reported. Survival outcomes – progression-free
(PFS) and overall (OS) – for the I and B randomizations are reported
here (To rand continued). The B randomization used a relaxed alpha (1-
sided p=0.2) for PFS as its phase 2 success criterion; the I randomiza-
tion was Bayesian. Cox model hazard ratios (HR) <1.0 indicate benefit
for I or B. Heterogeneity tests (HT) assessed interactions between B
and I. Analysis was intention-to-treat.
Results: From 2013-19, 160 patients were randomized to B v. no B,
including 121 to I v. no I, with median follow-up 15.4 months. B ran-
domization: HR (95%CI) for PFS and OS were 0.85(0.59-1.23) and
0.84(0.56-1.24) respectively. I randomization: HR (95%CI) for PFS and
OS were 0.66(0.43-1.00) and 0.63(0.41-0.99). I improved PFS and OS
(98% probability that true HR<1.0 for both) and B just met its success
criterion (PFS: 1p=0.20; OS: 1p=0.19).There was some, but not conclu-
sive, evidence of a positive interaction between B and I for both PFS
(HT:p=0.06) and OS (HT:p=0.12). If real, this would suggest that adding
either I (IT) or B (BT) to T does not improve outcome, but adding both
BIT) does.
Conclusions: The BEACON results show that single agent T is subopti-
mal. Statistical uncertainty about an interaction between I and B means
two further interpretations are possible: 1) IT and possibly BT are bet-
ter than T; 2) IT and BT are not better than T, but I and B together (BIT)
are better. Hence, a definitive conclusion on the best combination(s) to
take forward is not currently possible and further randomized evalua-
tion is needed
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Wheatley K, Holt G, Owens C, Valteau-Couanet D, Gambart M, Castel V, et al. Randomized comparisons of bevacizumab(B) and irinotecan(I),added to temozolomide(T), in children with relapsed/refractory high-risk neuroblastoma(RR-HRNB); survival results of the ITCC-SIOPEN beacon-neuroblastoma phase 2 trial. Pediatric Blood & Cancer. 2020;67:S31-S