First therapy approved for children with genetic tumor syndrome

2020

Challenge

Neurofibromatosis type 1 (NF1) is a rare, genetic tumor predisposition syndrome in children. About half of those with NF1 develop plexiform neurofibromas, which are debilitating tumors that grow along nerves and are typically first diagnosed at a very early age. Many plexiform neurofibromas grow relentlessly during early childhood, cannot be removed by surgery, and result in severe problems including disfigurement, chronic pain, breathing difficulties, and other symptoms, depending on the tumor’s location. The development of effective medical therapies for this illness has been an elusive goal.

Advance

After decades of research to understand and monitor the disease, IRP senior investigator Brigitte C. Widemann, M.D., led the seminal clinical trials that demonstrated the drug selumetinib (Koselugo™) shrank NF1-associated plexiform neurofibromas in the majority of patients and often reduced pain and improved overall quality of life.

Impact

Based on the results from Dr. Widemann’s trial, in April 2020, the U.S. Food and Drug Administration approved selumetinib as the first and only therapy for children two years and older with NF1 and symptomatic, inoperable plexiform neurofibromas. For her work on this breakthrough treatment, Dr. Widemann was named a finalist for the 2021 Samuel J. Heyman Service to America Medal, which honors exceptional work by government employees.

Publications

Gross AM, Wolters PL, Dombi E, Baldwin A, Whitcomb P, Fisher MJ, Weiss B, Kim A, Bornhorst M, Shah AC, Martin S, Roderick MC, Pichard DC, Carbonell A, Paul SM, Therrien J, Kapustina O, Heisey K, Clapp DW, Zhang C, Peer CJ, Figg WD, Smith M, Glod J, Blakeley JO, Steinberg SM, Venzon DJ, Doyle LA, Widemann BC. (2020). Selumetinib in Children with Inoperable Plexiform Neurofibromas. N Engl J Med. Apr 9;382(15):1430-1442. doi: 10.1056/NEJMoa1912735.

Akshintala S, Baldwin A, Liewehr DJ, Goodwin A, Blakeley JO, Gross AM, Steinberg SM, Dombi E, Widemann BC. (2020). Longitudinal evaluation of peripheral nerve sheath tumors in neurofibromatosis type 1: Growth analysis of plexiform neurofibromas and distinct nodular lesions. Neuro Oncol. Sep 29;22(9):1368-1378. doi: 10.1093/neuonc/noaa053.

Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC. (2016). Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med. Dec 29;375(26):2550-2560. doi: 10.1056/NEJMoa1605943.