J Clin Oncol: Efficacy of FAK inhibitors in recurrent or progressive NF2-mutant meningioma

Systemic therapy options are limited
for patients with progressive or recurrent meningioma.
Local adhesion kinase (FAK) inhibition is synthetically lethal to
NF2 loss.
Given the predominance of NF2 mutations in meningioma, the study evaluated the efficacy
of the FAK inhibitor GSK2256098 in patients with recurrent or progressive grade 1-3 meningioma.

Patients with NF2 mutation-positive meningiomas are treated with GSK2256098 (750 mg*2 times/day orally) until disease progression
.
The primary endpoints were progression-free survival (PFS6) and response rate
at six months.

6-month progression-free survival rate for cohorts at all levels

Of the 322 patients screened for all mutation cohorts, 36 patients with eligible, evaluable NF2 mutations were enrolled and treated: 12 patients with grade 1 meningiomas and 24 patients with
grade 2/3 meningiomas.
Of all patients with all grades of meningioma, one patient achieved a partial response and 24 remained stable
.
PFS6 in patients with grade 1 meningiomas is 83% (10/12).

PFS6 in patients with grade 2/3 meningiomas was 33% (8/24).

The study met PFS6 efficacy endpoints in both grade 1 and grade 2/3 patient cohorts
.

Optimal mitigation for each level of queue

GSK2256098 is well tolerated for treatment; Seven patients experienced the highest grade 3 adverse events, possibly related to treatment, and no grade 4 or 5 adverse events occurred
.

In summary, GSK2256098 is well tolerated compared to historical controls, improving 6-month progression-free survival in patients with recurrent or progressive NF2-mutant meningioma, and warrants further evaluation
.

Original source:

Priscilla K.
Brastianos, et al.
Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations.
Journal of Clinical Oncology.
October 26, 2022.
https://ascopubs.
org/doi/abs/10.
1200/JCO.
21.
02371?role=tab