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Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors.
Plotkin, Scott R; Yohay, Kaleb H; Nghiemphu, Phioanh L; Dinh, Christine T; Babovic-Vuksanovic, Dusica; Merker, Vanessa L; Bakker, Annette; Fell, Geoffrey; Trippa, Lorenzo; Blakeley, Jaishri O.
Affiliation
  • Plotkin SR; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Yohay KH; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Nghiemphu PL; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Dinh CT; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Babovic-Vuksanovic D; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Merker VL; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Bakker A; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Fell G; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Trippa L; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
  • Blakeley JO; From Massachusetts General Hospital and Harvard Medical School (S.R.P., V.L.M.) and the Dana-Farber Cancer Institute (G.F., L.T.) - all in Boston; the NYU Grossman School of Medicine (K.H.Y.) and the Children's Tumor Foundation (A.B.) - both in New York; the University of California, Los Angeles, Lo
N Engl J Med ; 390(24): 2284-2294, 2024 Jun 27.
Article in En | MEDLINE | ID: mdl-38904277
ABSTRACT

BACKGROUND:

NF2-related schwannomatosis (NF2-SWN, formerly called neurofibromatosis type 2) is a tumor predisposition syndrome that is manifested by multiple vestibular schwannomas, nonvestibular schwannomas, meningiomas, and ependymomas. The condition is relentlessly progressive with no approved therapies. On the basis of preclinical activity of brigatinib (an inhibitor of multiple tyrosine kinases) in NF2-driven nonvestibular schwannoma and meningioma, data were needed on the use of brigatinib in patients with multiple types of progressive NF2-SWN tumors.

METHODS:

In this phase 2 platform trial with a basket design, patients who were 12 years of age or older with NF2-SWN and progressive tumors were treated with oral brigatinib at a dose of 180 mg daily. A central review committee evaluated one target tumor and up to five nontarget tumors in each patient. The primary outcome was radiographic response in target tumors. Key secondary outcomes were safety, response rate in all tumors, hearing response, and patient-reported outcomes.

RESULTS:

A total of 40 patients (median age, 26 years) with progressive target tumors (10 vestibular schwannomas, 8 nonvestibular schwannomas, 20 meningiomas, and 2 ependymomas) received treatment with brigatinib. After a median follow-up of 10.4 months, the percentage of tumors with a radiographic response was 10% (95% confidence interval [CI], 3 to 24) for target tumors and 23% (95% CI, 16 to 30) for 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% (95% CI, 20 to 53) of eligible ears. Exploratory analyses suggested a decrease in self-reported pain severity during treatment (-0.013 units per month; 95% CI, -0.002 to -0.029) on a scale from 0 (no pain) to 3 (severe pain). No grade 4 or 5 treatment-related adverse events were reported.

CONCLUSIONS:

Brigatinib treatment resulted in radiographic responses in multiple tumor types and clinical benefit in a heavily pretreated cohort of patients with NF2-SWN. (Funded by the Children's Tumor Foundation and others; INTUITT-NF2 ClinicalTrials.gov number, NCT04374305.).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Organophosphorus Compounds / Pyrimidines / Skin Neoplasms / Neurilemmoma Limits: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Language: En Journal: N Engl J Med Year: 2024 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Organophosphorus Compounds / Pyrimidines / Skin Neoplasms / Neurilemmoma Limits: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Language: En Journal: N Engl J Med Year: 2024 Type: Article