Phase II Clinical Trial of Pasireotide Long-Acting Repeatable in Patients with Metastatic Neuroendocrine Tumors
Open accessAbstract
Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR 1,2,3 ) and 5 (SSTR 5 ). 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 SSTR 5 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. SSTR 5 expression is a potentially predictive biomarker for response.
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Pasireotide, an analog with higher affinity for SSTR5, has been associated with a median progression-free survival of 11 months in insulinomas.
“SSTR5 is the second most expressed receptor in insulinomas, and pasireotide, an analog with higher affinity for SSTR5, has been associated with a median progression-free survival of 11 months [93].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [93]
The Introduction says pasireotide has higher affinity for SSTR5 than octreotide, and Results > Progression-free and overall survival reports an overall median PFS of 11 months. That result is for patients with metastatic neuroendocrine tumors, not specifically insulinomas. The paper also does not establish that SSTR5 is the second most expressed receptor in insulinomas. Page numbers are not available in our copy. (LLM, conf=0.90)
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Cites
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“Pasireotide is a novel multireceptor-targeted SSA with avid binding affinity to four of the five SSTR subtypes (SSTR1,2,3 and SSTR5) (Schmid 2008).”
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Sorted by citations
Non-Diabetic Hypoglycemia: Evaluation and Management in Adults
Looi, E., & Lawler, H. M. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134393 · Cited by 10 · see citing works
“SSTR5 is the second most expressed receptor in insulinomas, and pasireotide, an analog with higher affinity for SSTR5, has been associated with a median progression-free survival of 11 months [93].”
- Authors
- Cives, M., Kunz, P. L., Morse, B., Coppola, D., Schell, M. J., Campos, T., Nguyen, P. T., Nandoskar, P., Khandelwal, V, & Strosberg, J. R.
- Affiliations
- Moffitt Cancer Center (US)
- Corresponding author
- Strosberg, J R
- Venue
- Endocrine-Related Cancer
- Publisher
- Bioscientifica
- Published
- 2014-11-06
- Volume
- 22
- Issue
- 1
- Pages
- 1-9
- ISSN
- 1351-0088 (ISSN-L)
- 1479-6821
- PMC
- PMC4643672
- OpenAlex
- W2322817866
- Cited by
- 96
- References
- 2
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 1 · 2021: 12 · 2020: 5 · 2019: 12 · 2018: 12 · 2017: 9 · 2016: 12 · 2015: 8 · 2013: 1
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Related Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- National Cancer Institute (P30CA076292, R25CA174664)
- Topics
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- somatostatin analogues, metastatic neuroendocrine tumors, somatostatin receptor 5, progression-free survival, hyperglycemia, predictive biomarkers, pancreatic neuroendocrine tumors, treatment-naive patients, first-line therapy
- MeSH terms
- Adult, Aged, Delayed-Action Preparations, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Pancreatic Neoplasms, Prospective Studies, Somatostatin, Receptors, Somatostatin, Neuroendocrine Tumors
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