pasireotide and Meningioma

Meningiomas represent the most common primary brain tumor and comprise 3 World Health Organization (WHO) grades, the most frequent being WHO grade I (90%). Surgery is mandatory to establish the diagnosis and to remove the tumor; however, complete resection can be achieved in only <50% of patients. Depending on the extent of resection, tumor location and the WHO grade radiation therapy can be applied. The issue of systemic treatment such as chemotherapy or targeted therapy (eg, somatostatin receptors, antiangiogenic agents) is yet not solved, particularly as current data are derived from small uncontrolled series in patients with long-standing disease and after several pretreatments. A more thorough understanding of molecular genetics, signaling pathways and prognostic factors in meningiomas should lead to the design of studies which stratify according to these factors. These studies have to be conducted in newly diagnosed patients after incomplete resection and in tumors of WHO grade II and III.

Topics: Antineoplastic Agents; Cranial Irradiation; Diagnostic Imaging; Endoscopy; Humans; Meningeal Neoplasms; Meningioma; Microsurgery; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Neuronavigation; Prognosis; Receptors, Somatostatin; Somatostatin

A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective.. Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B).. Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8-20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor-1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival.. Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation.. This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cohort Studies; Disease-Free Survival; Female; Humans; Insulin-Like Growth Factor I; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Recurrence, Local; Receptors, Somatostatin; Somatostatin