Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors.
Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response.
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Cives
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Kunz
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Morse
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Coppola
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Schell
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Campos
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Nguyen
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Nandoskar
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA.
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Khandelwal
Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USADepartment of MedicineStanford University School of Medicine, Stanford, California, USA jonathan.strosberg@moffitt.org.
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Strosberg
D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*
D003692:Delayed-Action Preparations; D017481:Receptors, Somatostatin; D013004:Somatostatin; C517782:pasireotide
carcinoid; neuroendocrine tumors; pasireotide; somatostatin analogs; somatostatin receptors