Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project

References

• Gurney JG, Smith MA, et al. Sympathetic nervous system tumors. In: Ries LAG, Smith MA, Gurney JG, editors. Cancer incidence and survival among children and adolescents: United States SEER program 1975–1995, National Cancer Institute, SEER program. Bethesda, MD: NIH Publication; 1999. p. 65–72.
   Google Scholar
• Maris JM, Hogarty MD, Bagatell R, et al. Neuroblastoma. Lancet. 2007;369:2106–2120.
   PubMed Web of Science ®Google Scholar
• Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363:1324–1334.
   PubMed Web of Science ®Google Scholar
• Matthay KK, Reynolds CP, Seeger RC, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 2009;27:1007–1013.
   PubMed Web of Science ®Google Scholar
• Pearson AD, Pinkerton CR, Lewis IJ, et al. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. Lancet Oncol. 2008;9:247–256.
   PubMed Web of Science ®Google Scholar
• Valteau-Couanet D, Le Deley MC, Bergeron C, et al. Long-term results of the combination of the N7 induction chemotherapy and the busulfan-melphalan high dose chemotherapy. Pediatr Blood Cancer. 2014;61(6):977–981.
   PubMed Web of Science ®Google Scholar
• London WB, Castel V, Monclair T, et al. Clinical and biologic features predictive of survival after relapse of neuroblastoma: a report from the International Neuroblastoma Risk Group project. J Clin Oncol. 2011;29:3286–3292.
   PubMed Web of Science ®Google Scholar
• Ladenstein R, Pötschger U, Hartman O, et al. 28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures. Bone Marrow Transplant. 2008;41(Suppl 2):S118–27.
   PubMed Web of Science ®Google Scholar
• Schrey D, Vaidya SJ, Levine D, et al. Additional therapies to improve metastatic response to induction therapy in children with high-risk neuroblastoma. J Pediatr Hematol Oncol. 2015;37(3):e150–e153.
   PubMed Web of Science ®Google Scholar
• Laverdiere C, Cheung NK, Kushner BH, et al. Long-term complications in survivors of advanced stage neuroblastoma. Pediatr Blood Cancer. 2005;45:324–332.
   PubMed Web of Science ®Google Scholar
• Moreno L, Vaidya SJ, Pinkerton CR, et al. Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience. Pediatr Blood Cancer. 2013;60:1135–1140.
   PubMed Web of Science ®Google Scholar
• Brodeur GM, Seeger RC, Schwab M, et al. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984;224:1121–1124.
   PubMed Web of Science ®Google Scholar
• Mosse YP, Laudenslager M, Longo L, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008;455:930–935.
   PubMed Web of Science ®Google Scholar
• Janoueix-Lerosey I, Lequin D, Brugières L, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature. 2008;455:967–970.
   PubMed Web of Science ®Google Scholar
• Chen Y, Takita J, Choi YL, et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature. 2008;455:971–974.
   PubMed Web of Science ®Google Scholar
• George RE, Sanda T, Hanna M, et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008;455:975–978.
   PubMed Web of Science ®Google Scholar
• Carr-Wilkinson J, O’Toole K, Wood KM, et al. High frequency of p53/MDM2/p14ARF pathway abnormalities in relapsed neuroblastoma. Clin Cancer Res. 2010;16:1108–1118.
   PubMed Web of Science ®Google Scholar
• Cheung NK, Zhang J, Lu C, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. Jama. 2012;307:1062–1071.
   PubMed Web of Science ®Google Scholar
• Valentijn LJ, Koster J, Zwijnenburg DA, et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet. 2015;47:1411–1414.
   PubMed Web of Science ®Google Scholar
• Peifer M, Hertwig F, Roels F, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015;526:700–704.
   PubMed Web of Science ®Google Scholar
• Eleveld TF, Oldridge DA, Bernard V, et al. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat Genet. 2015;47:864–871.
   PubMed Web of Science ®Google Scholar
• Pugh TJ, Morozova O, Attiyeh EF, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet. 2013;45:279–284.
   PubMed Web of Science ®Google Scholar
• Molenaar JJ, Koster J, Zwijnenburg DA, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature. 2012;483:589–593.
   PubMed Web of Science ®Google Scholar
• Moreno L, Marshall LV, Pearson AD. At the frontier of progress for paediatric oncology: the neuroblastoma paradigm. Br Med Bull. 2013;108:173–188.
   PubMed Web of Science ®Google Scholar
• Moreno L, Chesler L, Hargrave D, et al. Preclinical drug development for childhood cancer. Expert Opin Drug Discov. 2011;6:49–64.
   PubMed Web of Science ®Google Scholar
• Vassal G, Rousseau R, Blanc P, et al. Creating a unique, multi-stakeholder paediatric oncology platform to improve drug development for children and adolescents with cancer. Eur J Cancer. 2015;51:218–224.
   PubMed Web of Science ®Google Scholar
• Adamson PC, Houghton PJ, Perilongo G, et al. Drug discovery in paediatric oncology: roadblocks to progress. Nat Rev Clin Oncol. 2014;11:732–739.
   PubMed Web of Science ®Google Scholar
• Pearson AD, Herold R, Rousseau R, et al. Implementation of mechanism of action biology-driven early drug development for children with cancer. Eur J Cancer. 2016;62:124–131.
   PubMed Web of Science ®Google Scholar
• Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339:1546–1558.
   PubMed Web of Science ®Google Scholar
• Barone G, Anderson J, Pearson AD, et al. New strategies in neuroblastoma: therapeutic targeting of MYCN and ALK. Clin Cancer Res. 2013;19:5814–5821.
   PubMed Web of Science ®Google Scholar
• Mosse YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14:472–480.
   PubMed Web of Science ®Google Scholar
• Bresler SC, Wood AC, Haglund EA, et al. Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci Transl Med. 2011;3:108ra114.
   PubMed Web of Science ®Google Scholar
• Berry T, Luther W, Bhatnagar N, et al. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell. 2012;22:117–130.
   PubMed Web of Science ®Google Scholar
• Barone G, Tweddle DA, Shohet JM, et al. MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomakers and resistance. Curr Drug Targets. 2014;15:114–123.
   PubMed Web of Science ®Google Scholar
• Gamble LD, Kees UR, Tweddle DA, et al. MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63. Oncogene. 2012;31:752–763.
   PubMed Web of Science ®Google Scholar
• Rihani A, Vandesompele J, Speleman F, et al. Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. Cancer Cell Int. 2015;15:76.
   PubMed Web of Science ®Google Scholar
• Rader J, Russell MR, Hart LS, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013;19:6173–6182.
   PubMed Web of Science ®Google Scholar
• Amorim JP, Santos G, Vinagre J, et al. The role of ATRX in the alternative lengthening of telomeres (ALT) phenotype. Genes. 2016;7:pii: E66.
   PubMed Web of Science ®Google Scholar
• Geoerger B, Deschamps F, Puget S, et al. Molecular screening for cancer treatment optimization (MOSCATO 01) in pediatric patients: first feasibility results of a prospective molecular stratification trial. J Clin Oncol. 2014;32(supp: abstr 10500):10050.
   Google Scholar
• Worst BC, Van Tilburg CM, Balasubramanian GP, et al. Next-generation personalised medicine for high-risk paediatric cancer patients - the INFORM pilot study. Eur J Cancer. 2016;65:91–101.
   PubMed Web of Science ®Google Scholar
• Bosse KR, Maris JM. Advances in the translational genomics of neuroblastoma: from improving risk stratification and revealing novel biology to identifying actionable genomic alterations. Cancer. 2016;122:20–33.
   PubMed Web of Science ®Google Scholar
• TARGET – Neuroblastoma. [cited 2017 May 16]. Available from: https://ocg.cancer.gov/programs/target/projects/neuroblastoma
   Google Scholar
• Fransson S, Hansson M, Ruuth K, et al. Intragenic anaplastic lymphoma kinase (ALK) rearrangements: translocations as a novel mechanism of ALK activation in neuroblastoma tumors. Genes Chromosomes Cancer. 2015;54:99–109.
   PubMed Web of Science ®Google Scholar
• Schleiermacher G, Javanmardi N, Bernard V, et al. Emergence of new ALK mutations at relapse of neuroblastoma. J Clin Oncol. 2014;32:2727–2734.
   PubMed Web of Science ®Google Scholar
• Martinsson T, Eriksson T, Abrahamsson J, et al. Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumor progression and unresponsiveness to therapy. Cancer Res. 2011;71:98–105.
   PubMed Web of Science ®Google Scholar
• Combaret V, Iacono I, Bellini A, et al. Detection of tumor ALK status in neuroblastoma patients using peripheral blood. Cancer Med. 2015;4:540–550.
   PubMed Web of Science ®Google Scholar
• Collins I, Workman P. New approaches to molecular cancer therapeutics. Nat Chem Biol. 2006;2:689–700.
   PubMed Web of Science ®Google Scholar
• Goodwin R, Giaccone G, Calvert H, et al. Targeted agents: how to select the winners in preclinical and early clinical studies? Eur J Cancer. 2012;48:170–178.
   PubMed Web of Science ®Google Scholar
• Benson JD, Chen YN, Cornell-Kennon SA, et al. Validating cancer drug targets. Nature. 2006;441:451–456.
   PubMed Web of Science ®Google Scholar
• Puissant A, Frumm SM, Alexe G, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013;3:308–323.
   PubMed Web of Science ®Google Scholar
• Henssen A, Althoff K, Odersky A, et al. Targeting MYCN-driven transcription by BET-Bromodomain inhibition. Clin Cancer Res. 2016;22:2470–2481.
   PubMed Web of Science ®Google Scholar
• Gustafson WC, Meyerowitz JG, Nekritz EA, et al. Drugging MYCN through an allosteric transition in aurora kinase A. Cancer Cell. 2014;26:414–427.
   PubMed Web of Science ®Google Scholar
• Brockmann M, Poon E, Berry T, et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-MYC in childhood neuroblastoma. Cancer Cell. 2013;24:75–89.
   PubMed Web of Science ®Google Scholar
• Dauch D, Rudalska R, Cossa G, et al. A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer. Nat Med. 2016;22:744–753.
   PubMed Web of Science ®Google Scholar
• Beckers A, Van Peer G, Carter DR, et al. MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma. Cancer Lett. 2015;366:123–132.
   PubMed Web of Science ®Google Scholar
• Lopez JS, Banerji U. Combine and conquer: challenges for targeted therapy combinations in early phase trials. Nat Rev Clin Oncol. 2017;14:57–66.
   PubMed Web of Science ®Google Scholar
• Geoerger B, Schulte J, Zwaan CM, et al. Phase I study of ceritinib in pediatric patients with malignancies harboring a genetic alteration in ALK: safety, pharmacokinetic, and efficacy results. J Clin Oncol. 2015;33(suppl; abstr 10005):10005.
   PubMed Web of Science ®Google Scholar
• Mossé YP, Lipsitz E, Fox E, et al. Pediatric phase I trial and pharmacokinetic study of MLN8237, an investigational oral selective small-molecule inhibitor of aurora kinase A: a children’s oncology group phase I consortium study. Clin Cancer Res. 2012;18:6058–6064.
   PubMed Web of Science ®Google Scholar
• DuBois SG, Marachelian A, Fox E, et al. Phase I study of the aurora a kinase inhibitor alisertib in combination with irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma: A NANT (new approaches to neuroblastoma therapy) trial. J Clin Oncol. 2016;34:1368–1375.
   PubMed Web of Science ®Google Scholar
• Moreno L, Marshall LV, Pearson AD, et al. A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a cancer research UK study. Clin Cancer Re. 2015;21:267–273.
   PubMed Web of Science ®Google Scholar
• Novartis Pharmaceuticals. Phase I study of LDK378 in pediatric, malignancies with a genetic alteration in anaplastic lymphoma kinase (ALK). In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2012 [cited 2017 May 16]. ( NLM Identifier: NCT01742286) Available from: https://clinicaltrials.gov/ct2/show/NCT01742286
   Google Scholar
• Novartis Pharmaceutical. Ceritinib rare indications study in ALK+ tumors. In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2015 [cited 2017 May 16]. ( NLM Identifier: NCT02465528). Available from: https://clinicaltrials.gov/ct2/show/NCT02465528
   Google Scholar
• Ignyta, Inc. Study of RXDX-101 in children with recurrent or refractory solid tumors and primary CNS tumors, with or without TRK, ROS1, or ALK fusions. In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2016 [cited 2017 May 16]. ( NLM Identifier: NCT02650401). Available from: https://clinicaltrials.gov/ct2/show/NCT02650401
   Google Scholar
• Infarinato NR, Park JH, Krytska K, et al. The ALK/ROS1 inhibitor PF-06463922 overcomes primary resistance to crizotinib in ALK-driven neuroblastoma. Cancer Discov. 2016;6:96–107.
   PubMed Web of Science ®Google Scholar
• Guan J, Tucker ER, Wan H, et al. The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN. Dis Model Mech. 2016;9:941–952.
   PubMed Web of Science ®Google Scholar
• New Approaches to Neuroblastoma Therapy Consortium. Study of Lorlatinib (PF-06463922). In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2017 [cited 2017 May 16]. ( NLM Identifier: NCT03107988). Available from: https://clinicaltrials.gov/ct2/show/NCT03107988
   Google Scholar
• Fouladi M, Laningham F, Wu J, et al. Phase I study of everolimus in pediatric patients with refractory solid tumors. J Clin Oncol. 2007;25:4806–4812.
   PubMed Web of Science ®Google Scholar
• Geoerger B, Kieran MW, Grupp S, et al. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Eur J Cancer. 2012;48:253–262.
   PubMed Web of Science ®Google Scholar
• Spunt SL, Grupp SA, Vik TA, et al. Phase I study of temsirolimus in pediatric patients with recurrent/refractory solid tumors. J Clin Oncol. 2011;29:2933–2940.
   PubMed Web of Science ®Google Scholar
• Gore L, Trippett TM, Katzenstein HM, et al. A multicenter, first-in-pediatrics, phase 1, pharmacokinetic and pharmacodynamic study of ridaforolimus in patients with refractory solid tumors. Clin Cancer Res. 2013;19:3649–3658.
   PubMed Web of Science ®Google Scholar
• Pearson AD, Federico SM, Aerts I, et al. A phase I study of ridaforolimus (MK-8669) in pediatric patients with advanced solid tumors. Oncotarget. 2016;7:84736–84747.
   PubMed Web of Science ®Google Scholar
• Geoerger B, Bourdeaut F, DuBois SG, et al. Phase I study of LEE011 (CDK4/6 inhibitor) in patients with malignant rhabdoid tumours, neuroblastoma and cyclin D-CDK4/6 pathway-activated tumors. Clin Cancer Res. 2017. DOI:10.1158/1078-0432.CCR-16-2898.
   PubMed Web of Science ®Google Scholar
• Emory University. Abemaciclib in children with DIPG or recurrent/refractory solid tumors (AflacST1501). In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2015 [cited 2017 May 16]. ( NLM Identifier: NCT02644460). Available from: https://clinicaltrials.gov/ct2/show/NCT02644460
   Google Scholar
• Pediatric Brain Tumor Consortium. Palbociclib isethionate in treating younger patients with recurrent, progressive, or refractory central nervous system tumours. In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2014 [cited 2017 May 16]. ( NLM Identifier: NCT02255461). Available from: https://clinicaltrials.gov/ct2/show/NCT02255461
   Google Scholar
• New Approaches to Neuroblastoma Therapy Consortium. SF1126 for patients with relapsed or refractory neuroblastoma. In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2014 [cited 2017 May 16]. ( NLM Identifier: NCT02337309). Available from: https://clinicaltrials.gov/ct2/show/NCT02337309
   Google Scholar
• Paoletti X, Geoerger B, Doz F, et al. A comparative analysis of paediatric dose-finding trials of molecularly targeted agent with adults’ trials. Eur J Cancer. 2013;49:2392–2402.
   PubMed Web of Science ®Google Scholar
• Moreno L, Pearson ADJ, Paoletti X, et al. Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective. Nat Rev Clin Oncol. 2017 May 16. doi: 10.1038/nrclinonc.2017.59. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Onar-Thomas A, Xiong Z. A simulation-based comparison of the traditional method, rolling-6 design and a frequentist version of the continual reassessment method with special attention to trial duration in pediatric phase I oncology trials. Contemp Clin Trials. 2010;31:259–270.
   PubMed Web of Science ®Google Scholar
• Ensign LG, Gehan EA, Kamen DS, et al. An optimal three-stage design for phase II clinical trials. Stat Med. 1994;13:1727–1736.
   PubMed Web of Science ®Google Scholar
• Gustave Roussy, Cancer Campus, Grand Paris. European proof-of-concept therapeutic stratification trial of molecular anomalies in relapsed or refractory tumors (ESMART). In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2016 [cited 2017 May 16]. ( NLM Identifier: NCT02813135). Available from: https://clinicaltrials.gov/ct2/show/NCT02813135
   Google Scholar
• Kieran, M.W., Hargrave, D. R., Cohen, K. J., et al. Phase 1 study of dabrafenib in pediatric patients with relapsed or refractory BRAF V600E high- and low-grade gliomas, Langerhans cell histiocytosis, and other solid tumors. J Clin Oncol. 2015;33(suppl; abstr 10004):10004.
   Google Scholar
• GlaxoSmithKline. A study to determine safety, tolerability and pharmacokinetics of oral dabrafenib in children and adolescent subjects. In ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2012 [cited 2017 May 16]. ( NLM Identifier: NCT01677741). Available from: https://clinicaltrials.gov/ct2/show/NCT01677741
   Google Scholar
• Moroz V, Wilson JS, Kearns P, et al. Comparison of anticipated and actual control group outcomes in randomised trials in paediatric oncology provides evidence that historically controlled studies are biased in favour of the novel treatment. Trials. 2014;15:481.
   PubMed Web of Science ®Google Scholar
• Moreno L, Laidler J, Moroz V, et al. A randomised phase IIb trial of bevacizumab added to temozolomide ± irinotecan for children with refractory/relapsed neuroblastoma - BEACON-Neuroblastoma, a European Innovative Therapies for Children with Cancer (ITCC) - International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) trial. J Clin Oncol. 2015;33(suppl; abstr TPS10082):10082.
   PubMed Web of Science ®Google Scholar