Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial
Authors: 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. Tweddle, Giuseppe 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, Dominique Valteau-Couanet, Francisco José Bautista, Dermot Murphy, Guy Makin, Estelle Thebaut, Natasha van Eijkelenburg, Dave Hobin, Sucheta Vaidya, Martin Elliott, Gudrun Schleiermacher, Cormac Owens, Giuseppe Barone, Deborah Tweddle, Victoria Castel, Karsten Nysom, Julie Tandonnet, Nadege Corradini, Pascal Chastagner, Marion Gambart, Sarah Jannier, Aurora Castellano, Soledad Gallego, Carole Coze, Anne Auvrignon, Anne Sophie Defachelles, Ricardo Lopez Almaraz, Nicolas Gerber, Ruth Ladenstein, Bram De Wilde, Benedicte Brichard, Roberto Luksch, Michel Zwaan, Beck Popovic Maja, Courtney Willis, Juliet Gray, Simone Hettmer, Lothar Schweigerer, Udo Kontny, Holger Christiansen, Alberto Garaventa, Anthony Ng, Lisa Howell, Daniel Yeomanson
Journal: Journal of Clinical Oncology (2024)

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.