Journal article
Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations
Journal of clinical oncology, Vol.41(3), pp.618-628
01/20/2023
DOI: 10.1200/JCO.21.02371
PMCID: PMC9870228
PMID: 36288512
Abstract
Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with
loss. Given the predominance of
mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas.
Eligible patients whose tumors screened positively for
mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy.
Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with
mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events.
GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive
-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.
Details
- Title: Subtitle
- Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations
- Creators
- Priscilla K Brastianos - Massachusetts General HospitalErin L Twohy - Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN.Elizabeth R Gerstner - Massachusetts General HospitalTimothy J Kaufmann - Mayo Clinic, Rochester, MN.A John Iafrate - Massachusetts General HospitalJochen Lennerz - Massachusetts General HospitalSuriya Jeyapalan - Tufts Medical CenterDavid E Piccioni - University of California, San DiegoVarun Monga - University of IowaCamilo E Fadul - University of Virginia Medical CenterDavid Schiff - University of Virginia Medical CenterJennie W Taylor - University of California, San FranciscoSajeel A Chowdhary - Boca Raton Regional HospitalChetan Bettegowda - Johns Hopkins MedicineGeorge Ansstas - Washington University in St. LouisMacarena De La Fuente - University of Miami Health SystemMark D Anderson - University of Mississippi Medical CenterNicole Shonka - University of Nebraska Medical CenterDenise Damek - University of Colorado, Aurora, CO.Jose Carrillo - University of California, IrvineLara J Kunschner-Ronan - Dartmouth–Hitchcock Medical CenterRekha Chaudhary - University of CincinnatiKurt A Jaeckle - Mayo Clinic, Rochester, MN.Francis M Senecal - Northwest Medical SpecialtiesThomas Kaley - Memorial Sloan Kettering Cancer CenterTara Morrison - Lehigh Valley HospitalAlissa A Thomas - University of VermontMary R Welch - Columbia University Irving Medical CenterFabio Iwamoto - Columbia University Irving Medical CenterDavid Cachia - University of Massachusetts Chan Medical SchoolAdam L Cohen - Inova Health SystemShivangi Vora - The Ohio State UniversityMichael Knopp - The Ohio State UniversityIan F Dunn - University of OklahomaPriya Kumthekar - Northwestern UniversityJann Sarkaria - Mayo Clinic, Rochester, MN.Susan Geyer - Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN.Xiomara W Carrero - Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN.Maria Martinez-Lage - Massachusetts General HospitalDaniel P Cahill - Massachusetts General HospitalPaul D Brown - Mayo Clinic, Rochester, MN.Caterina Giannini - Mayo ClinicSandro Santagata - Brigham and Women's HospitalFrederick G Barker II - Harvard Medical SchoolEvanthia Galanis - Mayo Clinic, Rochester, MN.
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.41(3), pp.618-628
- DOI
- 10.1200/JCO.21.02371
- PMID
- 36288512
- PMCID
- PMC9870228
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- UG1 CA233320 / NCI NIH HHS U10 CA180821 / NCI NIH HHS UG1 CA233184 / NCI NIH HHS UG1 CA233331 / NCI NIH HHS U10 CA180882 / NCI NIH HHS UG1 CA233290 / NCI NIH HHS UG1 CA232760 / NCI NIH HHS UG1 CA233324 / NCI NIH HHS UG1 CA233339 / NCI NIH HHS UG1 CA233196 / NCI NIH HHS R37 CA225655 / NCI NIH HHS UG1 CA233193 / NCI NIH HHS U10 CA180888 / NCI NIH HHS UG1 CA233180 / NCI NIH HHS
- Language
- English
- Date published
- 01/20/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363314302771
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