Safety and efficacy of pasireotide (SOM230) in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR: Results of a phase II study

Abstract

4082 Background: Pasireotide is a novel multiligand somatostatin analogue that exhibits high binding affinity to 4 of 5 somatostatin receptor subtypes: sst1,2,3 and sst5. Compared with octreotide, pasireotide has 30, 5 and 40 times greater affinity for sst1,3 and sst5 receptors respectively and a comparable affinity for sst2. Methods: This was a Phase II, open-label, multicenter study in patients with metastatic carcinoid tumors whose symptoms (diarrhea and flushing) were inadequately controlled by octreotide LAR. Patients had histopathologically confirmed disease, elevated 5-HIAA and/or CgA levels and at least one measurable lesion (excluding bone). Patients initially received pasireotide 300 μg sc bid and escalated to a maximum dose of 1200 μg sc bid every 3 days until clinical response was achieved. Partial response (PR) was defined as a mean of <4 bowel movements (BM)/day with no more than 6 BM on any given day, and a mean of <2 flushing episodes/day for 15 consecutive days on a fixed dose of pasireotide. Complete response (CR) was defined as a mean of ≤3 BM/day, with no more than 3 BM on any given day, and no flushing episodes. Results: Safety data are reported from 45 patients as of September 2005; 44 patients (mean age 61 years) qualified for efficacy assessment. Carcinoid tumors were predominantly of midgut origin. Preliminary efficacy data in controlling symptoms of carcinoid syndrome showed PR in 9 patients (20%) at 600–1200 μg sc bid doses and CR in 2 patients (5%) at the 600 and 900 μg sc bid doses. Objective tumor response in 11 patients showed 9 with stable disease and 2 with progressive disease at 6 months. Adverse events (AEs) were primarily gastrointestinal (GI): abdominal pain (31%) and nausea (27%). Weight loss (22%) and fatigue (22%) were also reported. Most AEs were mild or moderate. Glucose-related AEs (predominantly CTC grade 1–2) were observed in 24% of patients. Most discontinuations were due to GI AEs (n = 6) or lack of therapeutic response. Conclusions: Pasireotide 600–1200 μg sc bid was effective in controlling symptoms of diarrhea and flushing in 25% of patients with metastatic carcinoid tumors inadequately controlled by octreotide LAR. The safety profile of pasireotide is similar to octreotide LAR. [Table: see text]