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

作者：Priscilla Kaliopi Brastianos, Erin L. Twohy, Elizabeth Robins Gerstner, Timothy J. Kaufmann, Anthony John Iafrate, Jochen K. Lennerz, Suriya A. Jeyapalan, David Eric Piccioni, Varun Monga, Camilo E. Fadul, David Schiff, Jennie Webster Taylor, Sajeel A. Chowdhary, Chetan Bettegowda, George Ansstas, Macarena I. de la Fuente, Mark Daniel Anderson, Nicole Shonka, Denise Damek, Jose Carrillo, Lara Kunschner Ronan, Rekha T. Chaudhary, Kurt A. Jaeckle, Francis Mark Senecal, Thomas Joseph Kaley, Tara Morrison, Alissa A. Thomas, Mary Roberta Welch, FABIO MASSAITI IWAMOTO, David Cachia, Adam Louis Cohen, Shivangi Vora, Michael Vinzenz Knopp, Ian F. Dunn, Priya Kumthekar, Jann Nagina Sarkaria, Susan Michelle Geyer, Xiomara W. Carrero, Maria Martinez‐Lage, Daniel P. Cahill, Paul David Brown, Caterina Giannini, Sandro Santagata, Frederick George Barker, Evanthia Galanis · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.21.02371 · 被引用次数：114 · 研究领域：Meningioma and schwannoma management、Neurofibromatosis and Schwannoma Cases、Vascular Malformations Diagnosis and Treatment

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 effi...