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

Lucas Moreno*, Rebekah Weston, Cormac Owens, Dominique Valteau-Couanet, Marion Gambart, Victoria Castel, C Michel Zwaan, Karsten Nysom, Nicolas Gerber, Aurora Castellano, Genevieve Laureys, Ruth Ladenstein, Jochen Rössler, Guy Makin, Dermot Murphy, Bruce Morland, Sucheta Vaidya, Estelle Thebaud, Natasha van Eijkelenburg, Deborah A TweddleGiuseppe Barone, Julie Tandonnet, Nadege Corradini, Pascal Chastagner, Catherine Paillard, Francisco J Bautista, Soledad Gallego Melcon, Bram De Wilde, Lynley Marshall, Juliet Gray, Susan A Burchill, Gudrun Schleiermacher, Louis Chesler, Andrew Peet, Martin O Leach, Kieran McHugh, Roisin Hayes, Neil Jerome, Hubert Caron, Jennifer Laidler, Nicola Fenwick, Grace Holt, Veronica Moroz, Pamela Kearns, Simon Gates, Andrew D J Pearson, Keith Wheatley, Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN)

*Corresponding author af dette arbejde
5 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol/bind42
Udgave nummer10
Sider (fra-til)1135-1145
Antal sider11
ISSN0732-183X
DOI
StatusUdgivet - 1 apr. 2024

Fingeraftryk

Dyk ned i forskningsemnerne om 'Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial'. Sammen danner de et unikt fingeraftryk.

Citationsformater