Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma

Abstract

Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective.

Methods: 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).

Results: 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.

Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation.

Classification of evidence: 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.

Figure 1. Progression-free survival

Kaplan-Meier curve showing progression-free survival stratified by cohort.

Figure 2. Percent change in IGF-1 levels

Plot showing percent change in IGF-1 level for each subject in whom serial IGF-1 measurements were obtained. IGF-1 = insulin-like growth factor–1.

Figure 3. SSTR immunohistochemical stains

Examples of spectrum of immunohistochemical staining for SSTRs in meningioma. (A) Hematoxylin & eosin showing typical grade 2 meningioma histology. (B) SSTR1 with no immunoreactivity (score 0). (C) Strong and homogeneous membranous expression of SSTR2, which was seen in a high percentage of cases (intensity and percentage score = 3). (D) Typical diffuse and moderate SSTR3 expression (intensity and percentage score = 3). (E) High power of (D) showing punctate and dot-like SSTR3 signal. (F) SSTR5 with moderate but diffuse signal (intensity and percentage score = 1). SSTR = somatostatin receptor.