Journal article
Temozolomide versus irinotecan-temozolomide for children with relapsed and refractory high risk neuroblastoma (RR-HRNB): Results of the BEACON-Neuroblastoma randomized phase 2 trial—A European Innovative Therapies for Children with Cancer (ITCC) - International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) trial.
- Moreno, Lucas Hospital Universitario Niño Jesús, Madrid, Spain;
- Moroz, Veronica University of Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham, United Kingdom;
- Owens, Cormac Pediatric Haematology/Oncology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland;
- Laidler, Jennifer University of Birmingham, Cancer Research Clinical Trials Unit, Birmingham, United Kingdom;
- Valteau-Couanet, Dominique Children and Adolescent Oncology Department, Gustave Roussy, Villejuif, France;
- Gambart, Marion CHU de Toulouse-Hôpital des Enfants, Toulouse, France;
- Castel, Victoria Hospital Universiario y Politecnico La Fe Valencia, Valencia, Spain;
- Van Eijkelenburg, Natasha Academic Medical Center Emma Childrens Hospital, Amsterdam, Netherlands;
- Castellano, Aurora Division of Oncology, Bambino Gesù Children's Hospital, Rome, Italy;
- Nysom, Karsten Rigshospitalet, Copenhagen, Denmark;
- Gerber, Nicolas U. University Children's Hospital, Zurich, Switzerland;
- Laureys, Genevieve Ghent University Hospital, Ghent, Belgium;
- Ladenstein, Ruth Lydia St. Anna Children's Hospital and Department of Paediatrics, Medical University Vienna, Vienna, Austria;
- Makin, Guy University of Manchester, Manchester, United Kingdom;
- Vaidya, Sucheta Royal Marsden Hospital, Sutton, United Kingdom;
- Thebaud, Estelle CHU Nantes-Hôpital Mère-Enfant, Nantes, France;
- Kearns, Pamela University of Birmingham, Birmingham, United Kingdom;
- Pearson, Andrew DJ The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom;
- Wheatley, Keith University of Birmingham, Birmingham, United Kingdom;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 10001-10001
English
10001 Background: BEACON-Neuroblastoma is a randomized Phase II trial to assess the activity of backbone chemotherapy regimens for children with RR-HRNB and to determine if inhibiting angiogenesis with bevacizumab adds to the activity of this chemotherapy. Methods: Patients aged 1-21 years with RR-HRNB with adequate organ function and performance status were randomized in a 2x2 factorial design to: temozolomide (T) versus irinotecan-temozolomide (IT), with or without bevacizumab. Here we report the results of the irinotecan randomization (T vs. IT), which had a probability-based Bayesian design. Primary endpoint was best overall response (complete or partial) during the first 6 courses, by RECIST for measurable disease patients and International Neuroblastoma Response Criteria for evaluable disease patients for which overall response rate (ORR) was calculated. Results: From 2013 to 2018, 61 patients were randomized to treatment with T and 60 to IT. Median age was 5.8 years. 85 and 36 had measurable and evaluable disease respectively; 55 and 66 had refractory and relapsed disease; 22 had MYCN amplification. Baseline characteristics were balanced between the arms. Response data was not yet available for 2 patients on T. Response was not assessable for 17 patients (did not have treatment or stopped early) who were considered non-responders. The ORR was 24% for T and 17% for IT (risk ratio (RR) = 0.70, 95% credible interval 0.32 to 1.44). The probability that the RR for ORR was >1.0 was 17%, meaning that IT did not show greater activity than T. There was no interaction between treatment with/without bevacizumab (heterogeneity test, p=0.7). 27 (44%) T and 35 (58%) IT patients had grade ≥3 toxicities as per CTCAE v4.0. Diarrhea occurred in no patients on T and 7 (12%) on IT; hematological toxicities included anemia (6 T, 4 IT), neutropenia (14 T, 22 IT) and thrombocytopenia (14 T, 11 IT). Conclusions: Irinotecan does not improve the response rate when added to temozolomide in RR-HRNB, but does increase diarrhea. Longer follow-up is needed before assessing whether it impacts progression-free or overall survival. Number of responses by treatment arm. Clinical trial information: NCT02308527. [Table: see text]
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1200/jco.2019.37.15_suppl.10001
- ISSN 0732-183X
- Persistent URL
- https://sonar.ch/global/documents/144502
Statistics
Document views: 31
File downloads: