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

每月一次帕瑞肽 LAR(SOM230C)治疗复发性或进行性脑膜瘤的 II 期研究

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作者:Andrew D Norden, Keith L Ligon, Samantha N Hammond, Alona Muzikansky, David A Reardon, Thomas J Kaley, Tracy T Batchelor, Scott R Plotkin, Jeffrey J Raizer, Eric T Wong, Jan Drappatz, Glenn J Lesser, Sam Haidar, Rameen Beroukhim, Eudocia Q Lee, Lisa Doherty, Debra Lafrankie, Sarah C Gaffey, Mary Ger

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.

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).

Objective

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

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.

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