Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas

New England Journal of Medicine

Volumn 375, Issue 26, 2016, Pages 2550-2560

  Dombi, Eva ^a   Baldwin, Andrea ^a   Marcus, Leigh J ^a,c   Fisher, Michael J ^d   Weiss, Brian ^f   Kim, Aerang ^e   Whitcomb, Patricia ^a   Martin, Staci ^a   Aschbacher Smith, Lindsey E ^f   Rizvi, Tilat A ^f   Wu, Jianqiang ^a   Ershler, Rachel ^a,c   Wolters, Pamela ^a   Therrien, Janet ^a   Glod, John ^a   Belasco, Jean B ^d   Schorry, Elizabeth ^f   Brofferio, Alessandra ^a   Starosta, Amy J ^a   Gillespie, Andrea ^a   Doyle, Austin L ^b   Ratner, Nancy ^f   Widemann, Brigitte C ^a   more..

^a NATIONAL CANCER INSTITUTE   (United States)

^b Cancer Therapy Evaluation Program   (United States)

^c CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e CHILDREN'S NATIONAL MEDICAL CENTER   (United States)

^f CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; CLINDAMYCIN; CREATINE KINASE; CREATINE KINASE MB; GLUCOCORTICOID; IMATINIB; LISINOPRIL; MITOGEN ACTIVATED PROTEIN KINASE; RETINOIC ACID; SELUMETINIB; TETRACYCLINE; BENZIMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PROTEIN KINASE INHIBITOR;

ACNEIFORM RASH; ADOLESCENT; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CATARACT; CELLULITIS; CHILD; CLINICAL ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DEFORMITY; DISEASE COURSE; DRUG ACTIVITY; DRUG DOSAGE FORM COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENZYME PHOSPHORYLATION; FEMALE; FUNCTIONAL DISEASE; GASTROINTESTINAL SYMPTOM; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; IMAGE ANALYSIS; LONG TERM CARE; MACULOPAPULAR RASH; MALE; MAXIMUM PLASMA CONCENTRATION; MOTOR PERFORMANCE; MOUSE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NEUROFIBROMA; NEUROFIBROMATOSIS TYPE 1; NEUTROPHIL COUNT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PAIN; PARONYCHIA; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PRESCHOOL CHILD; PRIORITY JOURNAL; RASH; RECOMMENDED DRUG DOSE; SCHOOL CHILD; SIDE EFFECT; TREATMENT DURATION; TREATMENT RESPONSE; TUMOR RELATED PAIN; TUMOR VOLUME; URTICARIA; ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; DIAGNOSTIC IMAGING; DISEASE MODEL; NEUROFIBROMA, PLEXIFORM; NEUROFIBROMATOSIS 1;

ADOLESCENT; ANIMALS; BENZIMIDAZOLES; CHILD; CHILD, PRESCHOOL; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; FEMALE; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; MICE; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NEUROFIBROMA, PLEXIFORM; NEUROFIBROMATOSIS 1; PROTEIN KINASE INHIBITORS;

EID: 85007327549     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1605943     Document Type: Article

References (43)

1. Ferner RE. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol 2007; 6: 340-51.
2. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13: 834-43.
3. Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 2002; 39: 311-4.
4. Kim A, Gillespie A, Dombi E, et al. Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas. Neurology 2009; 73: 1273-9.
5. Korf BR. Plexiform neurofibromas. Am J Med Genet 1999; 89: 31-7.
6. Mautner VF, Asuagbor FA, Dombi E, et al. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol 2008; 10: 593-8.
7. Nguyen R, Kluwe L, Fuensterer C, Kentsch M, Friedrich RE, Mautner VF. Plexiform neurofibromas in children with neurofibromatosis type 1: frequency and associated clinical deficits. J Pediatr 2011; 159(4): 652-5.e2.
8. Dombi E, Solomon J, Gillespie AJ, et al. NF1 plexiform neurofibroma growth rate by volumetric MRI: relationship to age and body weight. Neurology 2007; 68: 643-7.
9. Nguyen R, Dombi E, Widemann BC, et al. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis 2012; 7: 75.
10. Canavese F, Krajbich JI. Resection of plexiform neurofibromas in children with neurofibromatosis type 1. J Pediatr Orthop 2011; 31: 303-11.
11. Needle MN, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: the Children's Hospital of Philadelphia experience, 1974-1994. J Pediatr 1997; 131: 678-82.
12. Cichowski K, Jacks T. NF1 tumor suppressor gene function: narrowing the GAP. Cell 2001; 104: 593-604.
13. Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer 2015; 15: 290-301.
14. Weiss B, Bollag G, Shannon K. Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet 1999; 89: 14-22.
15. Gutmann DH, Blakeley JO, Korf BR, Packer RJ. Optimizing biologically targeted clinical trials for neurofibromatosis. Expert Opin Investig Drugs 2013; 22: 443-62.
16. Packer RJ, Gutmann DH, Rubenstein A, et al. Plexiform neurofibromas in NF1: toward biologic-based therapy. Neurology 2002; 58: 1461-70.
17. Widemann BC, Dombi E, Gillespie A, et al. Phase 2 randomized, flexible crossover, double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas. Neuro Oncol 2014; 16: 707-18.
18. Widemann BC, Babovic-Vuksanovic D, Dombi E, et al. Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas. Pediatr Blood Cancer 2014; 61: 1598-602.
19. Weiss B, Widemann BC, Wolters P, et al. Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study. Neuro Oncol 2015; 17: 596-603.
20. Weiss B, Widemann BC, Wolters P, et al. Sirolimus for non-progressive NF1-associated plexiform neurofibromas: an NF clinical trials consortium phase II study. Pediatr Blood Cancer 2014; 61: 982-6.
21. Jakacki RI, Dombi E, Steinberg SM, et al. Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas. Neuro Oncol 2016 August 10 (Epub ahead of print).
22. Robertson KA, Nalepa G, Yang FC, et al. Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial. Lancet Oncol 2012; 13: 1218-24.
23. Wu J, Dombi E, Jousma E, et al. Preclinical testing of sorafenib and RAD001 in the Nf(flox/flox);DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging. Pediatr Blood Cancer 2012; 58: 173-80.
24. Wu J, Williams JP, Rizvi TA, et al. Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell 2008; 13: 105-16.
25. Yang FC, Ingram DA, Chen S, et al. Nf1-dependent tumors require a microenvironment containing Nf1+/- and c-kit- dependent bone marrow. Cell 2008; 135: 437-48.
26. Lauchle JO, Kim D, Le DT, et al. Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras. Nature 2009; 461: 411-4.
27. Jessen WJ, Miller SJ, Jousma E, et al. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Invest 2013; 123: 340-7.
28. Ho AL, Grewal RK, Leboeuf R, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med 2013; 368: 623-32.
29. Jänne PA, Shaw AT, Pereira JR, et al. Selumetinib plus docetaxel for KRASmutant advanced non-small-cell lung cancer: a randomised, multicentre, placebocontrolled, phase 2 study. Lancet Oncol 2013; 14: 38-47.
30. Robert C, Dummer R, Gutzmer R, et al. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol 2013; 14: 733-40.
31. National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987. Neurofibromatosis 1988; 1: 172-8.
32. Dombi E, Ardern-Holmes SL, Babovic-Vuksanovic D, et al. Recommendations for imaging tumor response in neurofibromatosis clinical trials. Neurology 2013; 81: S33-40.
33. Smith M, Bernstein M, Bleyer WA, et al. Conduct of phase I trials in children with cancer. J Clin Oncol 1998; 16: 966-78.
34. Riekert K. Health beliefs and medication adherence. Cleveland: Case Western Reserve University, 2001 (Ph.D. thesis).
35. Solomon J, Warren K, Dombi E, Patronas N, Widemann B. Automated detection and volume measurement of plexiform neurofibromas in neurofibromatosis 1 using magnetic resonance imaging. Comput Med Imaging Graph 2004; 28: 257-65.
36. Estey E, Hoth D, Simon R, Marsoni S, Leyland-Jones B, Wittes R. Therapeutic response in phase I trials of antineoplastic agents. Cancer Treat Rep 1986; 70: 1105-15.
37. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000; 92: 205-16.
38. Banerji U, Camidge DR, Verheul HM, et al. The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): a phase I open-label multicenter trial in patients with advanced cancer. Clin Cancer Res 2010; 16: 1613-23.
39. Widemann BC, Salzer WL, Arceci RJ, et al. Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. J Clin Oncol 2006; 24: 507-16.
40. Banerjee A, Jakacki R, Onar-Thomas A, et al. A phase 1 study of AZD6244 in children with recurrent or refractory low-grade gliomas: a Pediatric Brain Tumor Consortium report. J Clin Oncol 2014; 32(Suppl): 5s. abstract.
41. Balagula Y, Barth Huston K, Busam KJ, Lacouture ME, Chapman PB, Myskowski PL. Dermatologic side effects associated with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886). Invest New Drugs 2011; 29: 1114-21.
42. Infante JR, Fecher LA, Falchook GS, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol 2012; 13: 773-81.
43. Beert E, Brems H, Daniëls B, et al. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer 2011; 50: 1021-32.