Verzenio Shows Activity in High-Grade Meningioma

Patients with recurrent or progressive high-grade meningiomas with CDK pathway or NF2 genetic alterations showed encouraging responses to the targeted therapy Verzenio (abemaciclib), according to trial data published in Nature Medicine.

The study, part of Alliance A071401, aimed to evaluate whether Verzenio could slow disease progression and was designed to support further investigation in this patient population.

Study results of Verzenio Treatment for high-grade meningiomas

Among the first 24 patients evaluated, 14 patients were progression-free and alive at six months. The primary measure, progression-free survival at six months (PFS6), was successfully met according to the trial’s prespecified criteria, which required at least eight patients to be progression-free at that time point. Stable disease was the best response, observed in 16 of 24 patients, while no complete or partial responses were recorded. Central radiology review of 21 patients confirmed that 12 patients were progression-free at six months based on Macdonald criteria and volumetric measurements.

The median overall survival was 29.1 months for the first 24 evaluable patients and remained the same when all 35 evaluable patients were included. Median progression-free survival was 10.1 months for the first 24 patients and 7.6 months for all evaluable patients. Among patients whose best response was stable disease, median progression-free survival extended to 11.1 months.

Exploratory analyses showed patients with NF2 alterations had higher PFS6 outcomes (15 of 24) compared to those with CDK pathway alterations alone (one of four) or combined NF2 and CDK pathway alterations (two of seven). Patients with NF2 alterations also had longer median progression-free survival of 12.1 months compared with 2.4 months for CDK pathway patients and two months for those with both alterations. Immunohistochemistry and genetic analyses suggested higher mean p16 levels in patients who clinically benefited from Verzenio.

Trial details of Alliance A071401

Alliance A071401 is a multi-arm, genomically driven phase 2 study of targeted therapies for patients with specific genetic mutations. Eligible patients had recurrent or progressive grade 2 or 3 meningiomas, measurable disease, and either CDK pathway or NF2 alterations in their tumor tissue. All participants had previously undergone surgery, and most had received radiation and other medical therapies.

Verzenio was given orally at 200 milligrams (mg) twice daily in 28-day cycles until disease progression, unacceptable toxicity, neurological deterioration or study withdrawal. Patients underwent MRI scans every eight weeks, and disease response was evaluated using Macdonald criteria. Co-primary endpoints included PFS6 and response rate, while secondary endpoints included overall survival, progression-free survival, toxicity and central radiology review outcomes. Exploratory endpoints assessed genetic and histological biomarkers of response.

Safety

All 36 patients who started treatment were evaluated for safety. The average number of treatment cycles received was nine. Twelve patients experienced at least one treatment delay. Seven patients discontinued Verzenio due to side effects, and nine patients experienced grade 3 (severe) side effects. Two patients experienced grade 4 (life-threatening) events, including elevated liver enzymes (AST/ALT) and vomiting, which were at least possibly related to treatment.

Overall, Verzenio was well tolerated, with side effects manageable through dose adjustments and treatment breaks, supporting further research in patients with high-grade meningiomas harboring CDK pathway or NF2 alterations.

Reference

1. “Genomically driven trials for patients with meningioma” by Dr Priscilla K. Brastianos, et al., Nature Medicine.

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