Multicenter phase 2 trial of brigatinib in NF2-related schwannomatosis with progressive tumors

NF2-related schwannomatosis (NF2-SWN; formerly called neurofibromatosis type 2) is a tumor predisposition syndrome that is manifested by multiple vestibular schannomas, nonvestibular schwannomas, meningiomas, and ependymomas. The condition is progressive with no approved therapies. The multicenter phase 2 INTUITT-NF2 trial in the USA evaluated brigatinib 180 mg daily for NF2-SWN in heavily pretreated patients. The treatment resulted radiographic responses in 10% of target tumors and 23% of all tumors; meningiomas and nonvestibular schwannomas had the greatest benefit. Annualized growth rates decreased for all tumor types during treatment. Hearing improvement occurred in 35% of eligible ears. Exploratory analyses suggested a decrease in patient-reported pain. There were no grade 4 or 5 treatment-related adverse events. The authors conclude that brigatinib treatmen resulted in radiographic response in multiple tumor types and clinical benefit in a cohort of heavily pretreated patients with NF2-SWN.