Poster Presentation Advances in Neuroblastoma Research Congress 2016

The BEACON-Neuroblastoma ITCC/SIOPEN phase 2 trial for children with relapsed and refractory neuroblastoma: a progress report (#224)

Lucas Moreno 1 , Veronica Moroz 2 , Cormac Owens 3 , Jennifer Laidler 2 , Marion Gambart 4 , Aurora Castellano 5 , Pablo Berlanga 6 , Ruth Ladenstein 7 , Michel Zwaan 8 , Karsten Nysom 9 , Jochen Roessler 10 , Sucheta Vaidya 11 , Bruce Morland 12 , Martin Elliott 13 , Guy Makin 14 , Quentin Campbell-Hewson 15 , Pascal Chastagner 16 , Gudrun Schleiermacher 17 , Louis Chesler 18 , Susan Burchill 19 , Lynley Marshall 11 , Neil Jerome 18 , Dominique Valteau-Couanet 20 , Pamela Kearns 2 , Andrew DJ Pearson 18 , Keith Wheatley 2
  1. Hospital Infantil Universitario Nino Jesus, Madrid, Spain
  2. Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
  3. Our Lady Children's Hospital, Dublin, Ireland
  4. Hospital des Enfants, CHU Toulouse, Toulouse, France
  5. Ospedale Bambino Gesu, Rome, Italy
  6. Instituto de Investigacion Sanitaria La Fe, Valencia, Spain
  7. CCRI, Vienna, Austria
  8. Erasmus Medical Centre-Sophia Children’s Hospital, Rotterdam, The Netherlands
  9. Rigshospitalet, Copenhagen, Denmark
  10. University of Freiburg, Freigurb, Germany
  11. Royal Marsden Hospital, Sutton, UK
  12. Birmingham Children's Hospital, Birmingham, UK
  13. Leeds General Infirmary, Leeds, UK
  14. Manchester Academic Health Science Centre, Manchester, UK
  15. Royal Victoria Infirmary, Newcastle, UK
  16. Hopital des Enfants, CHRU Nancy, Nancy, France
  17. Institut Curie, Paris, France
  18. The Institute of Cancer Research, London, uk
  19. St.James University Hospital, Leeds, UK
  20. Institut Gustave Roussy, Villejuif, France

Background: Current therapy for relapsed/refractory neuroblastoma is not evidence based. Long-term disease control is poor and there is a need for randomised controlled trials (RCT). BEACON-Neuroblastoma is the first randomized European study for relapsed/refractory neuroblastoma and is a critical element of the SIOPEN/ITCC strategy for the development of new agents

Patients and Methods: Factorial phase 2, European, open-label, RCT (EudraCT 2012-000072-42) sponsored by the University of Birmingham, UK, that will evaluate the role of bevacizumab (B) and three backbone chemotherapy regimens (temozolomide (T), irinotecan(I)-temozolomide and topotecan(To)-temozolomide) relapsed/refractory neuroblastoma. The trial incorporates molecular characterisation, functional imaging to elucidate the role of anti-angiogenic therapy, measurement of neuroblastoma mRNAs and is due to be completed in 2017.

Results: As of January 2016, 65 patients have been randomized to T (16), BT (17), IT (15), BIT (16) and BTTo (1) from 26 sites in 8 European countries. Patients had refractory (35), early (22) or late (8) relapsed neuroblastoma. Median age was 5.7 (range 1.6-21.2) years and MYCN amplification was present in 22%. Thirty nine of 50 cases with available data had measurable disease per RECIST, 49 had MIBG positive disease and 24 had bone marrow involvement. Most common sites of disease were bone, bone marrow and primary tumor. Progression-free survival (PFS) at 6 and 12 months is 57% (95% CI: 40%-70%) and 36% (CI: 18%-55%); overall survival is 77% (CI: 61% to 87%) and 52% (CI: 29%-71%) respectively. 6-monthPFS is: 50% (CI: 25%-71%) and 63% (CI: 41%-79%) for relapsed versus refractory neuroblastoma; 51% (CI: 19%-76%) and 57% (CI: 36%-72%) for MYCN amplified versus non-amplified patients.

Conclusions: The BEACON-Neuroblastoma trial has established a network and infrastructure to evaluate new drugs efficiently in Europe and will provide reliable evidence on treatments for relapsed/refractory NBL. The results will inform the design of future relapse and frontline studies.