Andrew D Norden1, Keith L Ligon1, Samantha N Hammond1, Alona Muzikansky1, David A Reardon1, Thomas J Kaley1, Tracy T Batchelor1, Scott R Plotkin1, Jeffrey J Raizer1, Eric T Wong1, Jan Drappatz1, Glenn J Lesser1, Sam Haidar1, Rameen Beroukhim1, Eudocia Q Lee1, Lisa Doherty1, Debra Lafrankie1, Sarah C Gaffey1, Mary Gerard1, Katrina H Smith1, Christine McCluskey1, Surasak Phuphanich1, Patrick Y Wen2. 1. From the Division of Cancer Neurology, Department of Neurology (A.D.N., E.Q.L., P.Y.W.), and Departments of Pathology (K.L.L.) and Medicine (R.B.), Brigham and Women's Hospital, Boston, MA; Center for Neuro-Oncology (A.D.N., S.N.H., D.A.R., R.B., E.Q.L., L.D., D.L., M.G., K.H.S., C.M., P.Y.W.), Dana-Farber/Brigham and Women's Cancer Center; Department of Medicine (R.B.), Harvard Medical School (A.D.N., K.L.L., D.A.R., T.T.B., S.R.P., E.T.W., R.B., E.Q.L., P.Y.W.), Boston; Department of Medical Oncology, Center for Molecular Oncologic Pathology (K.L.L., S.H.), and Departments of Medical Oncology and Cancer Biology (R.B.), Dana-Farber Cancer Institute, Boston; Massachusetts General Hospital Biostatistics Center (A.M.); Brain Tumor Center (T.J.K.), Memorial Sloan-Kettering Cancer Center, New York, NY; Pappas Center for Neuro-Oncology (T.T.B., S.R.P.), Massachusetts General Hospital, Boston; Department of Neurology (J.J.R.), Northwestern University Feinberg School of Medicine, Chicago, IL; Brain Tumor Center (E.T.W.), Beth-Israel Deaconess Medical Center, Boston; Adult Neuro-Oncology Program (J.D.), University of Pittsburgh Medical Center, Pittsburgh, PA; Comprehensive Cancer Center (G.J.L.), Wake Forest University Baptist Medical Center, Winston-Salem, NC; and Departments of Neurosurgery and Neurology (S.P.), Cedars-Sinai Medical Center, Los Angeles, CA. 2. From the Division of Cancer Neurology, Department of Neurology (A.D.N., E.Q.L., P.Y.W.), and Departments of Pathology (K.L.L.) and Medicine (R.B.), Brigham and Women's Hospital, Boston, MA; Center for Neuro-Oncology (A.D.N., S.N.H., D.A.R., R.B., E.Q.L., L.D., D.L., M.G., K.H.S., C.M., P.Y.W.), Dana-Farber/Brigham and Women's Cancer Center; Department of Medicine (R.B.), Harvard Medical School (A.D.N., K.L.L., D.A.R., T.T.B., S.R.P., E.T.W., R.B., E.Q.L., P.Y.W.), Boston; Department of Medical Oncology, Center for Molecular Oncologic Pathology (K.L.L., S.H.), and Departments of Medical Oncology and Cancer Biology (R.B.), Dana-Farber Cancer Institute, Boston; Massachusetts General Hospital Biostatistics Center (A.M.); Brain Tumor Center (T.J.K.), Memorial Sloan-Kettering Cancer Center, New York, NY; Pappas Center for Neuro-Oncology (T.T.B., S.R.P.), Massachusetts General Hospital, Boston; Department of Neurology (J.J.R.), Northwestern University Feinberg School of Medicine, Chicago, IL; Brain Tumor Center (E.T.W.), Beth-Israel Deaconess Medical Center, Boston; Adult Neuro-Oncology Program (J.D.), University of Pittsburgh Medical Center, Pittsburgh, PA; Comprehensive Cancer Center (G.J.L.), Wake Forest University Baptist Medical Center, Winston-Salem, NC; and Departments of Neurosurgery and Neurology (S.P.), Cedars-Sinai Medical Center, Los Angeles, CA. pwen@partners.org.
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.
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.
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