Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Progression Free Survival (PFS) of patients with recurrent or progressive benign and atypical/malignant Meningiomas (grades I-III), despite prior therapy treated with bevacizumab will be defined from the time of registration to the study until the time of first documentation of progressive disease or death from any cause. Progressive disease will be assessed based on the Macdonald Criteria and is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Time frame: From the start of treatment and up until 6 months of treatment or follow up

Population: PFS was analyzed based on grading of meningioma due to the difference in prognosis of grades to provide meaningful results. In general, grade I tumor grows slowly, grade II tumor grows more quickly and is often called atypical meningioma, and grade III tumor grows and spreads very quickly and is often called anaplastic or malignant meningioma.

Tissue was collected for VEGF, VEGRfR2 and HER2 at baseline. Patients underwent radiological assessments every 8 weeks during treatment to determine disease status to treatment (complete response/partial response/stable disease/progressive disease). The level of VEGF, VEGRfR2 and HER2 marker expression was compared with the response as determined at the time of disease progression or death. Immunohistochemistry (IHC) will be analyzed using blobfinder technology. Each sample was given a score for the markers expression in the tissue 1, 2 or 3 (1=+, 2=++, 3=+++, from low to high) and a percentage 0-100% (low to high) of how much tissue it was expressed in. If score = 0 and percentage =0 the sample was negative for that marker. If score = 1 and percentage =10% the marker had an expression of 1 (+) in 10 percent of the tissue and so forth. The data is shown by patient and their best response to treatment with their score and expression for VEGF, VEGRfR2 and HER2.

Time frame: At baseline and every 8 weeks until disease progression or death. The maximum duration any one patient was on treatment was approximately 5 years.

Overall Survival (OS) of patients with Recurrent or Progressive Meningiomas Treated with Bevacizumab will be measured from the time of treatment initiation to the study until death from any cause. The raw data of number of patients documented as being alive at 1 year, 2 year, and 3 years post treatment initiation is reported here.

Time frame: At 1 year, 2 years, 3 years post treatment initiation

Population: 2 patients were considered lost to follow up at year 2 and year 3 respectively and were not included in the numbers. Data cut off was Dec 2018 and those who had not reached 3 years are not included in the 3 year number of patients alive. No survival data was collected at these timepoints.

Best Response of patients treated with bevacizumab with diagnosis of any of the following: meningioma, hemangiopericytoma, hemangioblastoma, acustic neuroma or schwanoma will be assessed using the MacDonald Criteria. In general: Complete Response-Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients not on steroids. Partial Response-50% or greater decrease under baseline in the sum of products of perpendicular diameters of the two largest measurable lesions. No progression of evaluable disease. No new lesions. Stable Disease-Not CR or PR or PD. Progressive disease (PD)-25% increase in the sum of products of all measurable lesions over smallest sum observed, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear worsening or failure to return for evaluation due to death/deteriorating condition

Time frame: From start of treatment and approximately every 8 weeks for up to approximately 5 years ( maximum duration any one patient was on treatment)

Safety of bevacizumab in patients with diagnosis of any of the following: meningioma, hemangiopericytoma, hemangioblastoma, acustic neuroma or schwanoma, will be assessed by collecting the number of adverse events experienced by patients that were determined to be at least possibly related to bevacaumab and assessed as a grade 3 or 4. AEs will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. In general, AEs will be graded as follows: Grade 1 - Mild Grade 2 - Moderate Grade 3 - Severe Grade 4 - Life-threatening Grade 5 - Fatal

Time frame: Every 2 weeks or 3 weeks while on treatment up to 30 days after the last dose. The maximum duration any one patient was on treatment was approximately 5 years.