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.