Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations.

Autor:	Brastianos PK; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Twohy EL; Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN., Gerstner ER; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Kaufmann TJ; Mayo Clinic, Rochester, MN., Iafrate AJ; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Lennerz J; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Jeyapalan S; Tufts Medical Center, Boston, MA., Piccioni DE; UC San Diego, San Diego, CA., Monga V; University of Iowa, Iowa City, IA., Fadul CE; University of Virginia Medical Center, Charlottesville, VA., Schiff D; University of Virginia Medical Center, Charlottesville, VA., Taylor JW; University of California, San Francisco Brain Tumor Center, San Francisco, CA., Chowdhary SA; Lynn Cancer Institute, Boca Raton Regional Hospital/Baptist Hospital South Florida, Boca Raton, FL., Bettegowda C; Johns Hopkins University School of Medicine, Baltimore, MD., Ansstas G; Washington University in St Louis, St Louis, MO., De La Fuente M; University of Miami Health System, Miami, FL., Anderson MD; University of Mississippi Medical Center, Jackson, MS., Shonka N; University of Nebraska Medical Center, Omaha, NE., Damek D; University of Colorado, Aurora, CO., Carrillo J; University of California Irvine, Irvine, CA., Kunschner-Ronan LJ; Dartmouth-Hitchcock Medical Center, Lebanon, NH., Chaudhary R; University of Cincinnati, West Chester, OH., Jaeckle KA; Mayo Clinic, Rochester, MN., Senecal FM; Northwest Medical Specialties, PLLC, Tacoma, WA., Kaley T; Memorial Sloan Kettering Cancer Center, New York, NY., Morrison T; Lehigh Valley Hospital-Cedar Crest, Allentown, PA., Thomas AA; University of Vermont, Burlington, VT., Welch MR; Columbia University Irving Medical Center, New York, NY., Iwamoto F; Columbia University Irving Medical Center, New York, NY., Cachia D; University of Massachusetts, Worcester, MA., Cohen AL; Inova Schar Cancer Institute, Fairfax, Virginia., Vora S; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Knopp M; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Dunn IF; College of Medicine, University of Oklahoma, Oklahoma City, OK., Kumthekar P; Northwestern University, Chicago, IL., Sarkaria J; Mayo Clinic, Rochester, MN., Geyer S; Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN., Carrero XW; Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN., Martinez-Lage M; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Cahill DP; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Brown PD; Mayo Clinic, Rochester, MN., Giannini C; Mayo Clinic, Rochester, MN., Santagata S; Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Barker FG 2nd; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Galanis E; Mayo Clinic, Rochester, MN.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Jan 20; Vol. 41 (3), pp. 618-628. Date of Electronic Publication: 2022 Oct 26.
DOI:	10.1200/JCO.21.02371
Abstrakt:	Purpose: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 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. Patients and Methods: Eligible patients whose tumors screened positively for NF2 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. Results: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 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. Conclusion: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2 -mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.
Databáze:	MEDLINE
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