Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations.
Обработка статьи · этапы, ошибки и управление
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Brastianos Priscilla K, Twohy Erin L, Gerstner Elizabeth R, Kaufmann Timothy J, Iafrate A John, Lennerz Jochen, Jeyapalan Suriya, Piccioni David E, Monga Varun, Fadul Camilo E, Schiff David, Taylor Jennie W, Chowdhary Sajeel A, Bettegowda Chetan, Ansstas George, De La Fuente Macarena, Anderson Mark D, Shonka Nicole, Damek Denise, Carrillo Jose, Kunschner-Ronan Lara J, Chaudhary Rekha, Jaeckle Kurt A, Senecal Francis M, Kaley Thomas, Morrison Tara, Thomas Alissa A, Welch Mary R, Iwamoto Fabio, Cachia David, Cohen Adam L, Vora Shivangi, Knopp Michael, Dunn Ian F, Kumthekar Priya, Sarkaria Jann, Geyer Susan, Carrero Xiomara W, Martinez-Lage Maria, Cahill Daniel P, Brown Paul D, Giannini Caterina, Santagata Sandro, Barker Frederick G, Galanis Evanthia
Аннотация
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.