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Focal Adhesion Kinase Inhibitor in Patients With Meningioma and Somatic NF2 Mutations


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As reported in the Journal of Clinical Oncology by Priscilla K. Brastianos, MD, PhD, and colleagues, the phase II Alliance A071401 trial showed activity of the focal adhesion kinase (FAK) inhibitor GSK2256098 in patients with recurrent or progressive grade 1 to 3 meningioma and somatic NF2 mutations.

As stated by the investigators, “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 to 3 meningiomas.”

Priscilla K. Brastianos, MD, PhD

Priscilla K. Brastianos, MD, PhD

Study Details

In the multicenter study, 36 eligible and evaluable patients, enrolled between August 2015 and July 2017, received oral GSK2256098 at 750 mg twice daily until progressive disease or unacceptable toxicity. Overall, 12 patients had grade 1 disease and 24 had grade 2/3 disease.

The co-primary endpoints were (1) 6-month progression-free survival, evaluated separately in grade 1 and grade 2/3 disease, and (2) rate of response. For the first endpoint, the treatment would be considered to have promising activity if 6-month progression-free survival were observed in 7 of 12 patients (at least 58%) with grade 1 disease (vs a null hypothesis of 25%, based on findings in historical controls) or in 8 of 32 (at least 33%) with grade 2/3 disease (vs null hypothesis of 15%).

Activity

Among all patients, partial response was observed in 1 patient (3%; grade 2/3 cohort) and stable disease was observed in 24 (67%), including 10 (83%) in the grade 1 cohort and 14 (58%) in the grade 2/3 cohort.

Among patients with grade 1 disease, 6-month progression-free survival was observed in 10 (83%, 95% confidence interval [CI] = 52%–98%) of 12 patients. Among those with grade 2/3 disease, 6-month progression-free survival was observed in 8 (33%, 95% CI = 16%–55%) of 24. The predefined criteria for promising activity were thus met in both cohorts.

KEY POINTS

  • Objective response was observed in 3% of patients and stable disease was seen in 67%.
  • 6-month progression-free survival rates were 83% among patients with grade 1 disease and 33% among those with grade 2/3 disease.

Adverse Events

Among 37 patients in the safety analysis, grade 3 adverse events (no grade 4 or 5 events observed) were observed in 15 patients (41%) and were considered related to treatment in 7 (19%); treatment-related events consisted of proteinuria, pain, lymphopenia, rash, nervous system disorder, transaminase elevation, cholecystitis, and hypertriglyceridemia. Treatment was discontinued due to adverse events or complications in four patients (11%). 

The investigators concluded, “GSK2256098 was well tolerated and resulted in an improved 6-month progression-free survival 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.”

Dr. Brastianos, of Massachusetts General Hospital Cancer Center, Harvard Medical School, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute, AstraZeneca, Eli Lilly, GSK (Novartis), and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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