Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4082
© 2006 American Society of Clinical Oncology

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Abstract

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

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Universitatsklinikum, Berlin, Germany; University Hospital, Uppsala, Sweden; Novartis Pharmaceuticals Corporation, East Hanover, NJ; University of Iowa, Iowa City, IA; Erasmus Medical Center, Rotterdam, The Netherlands; Philipps-Universitat, Marburg, Germany; Louisiana State University Medical Center, New Orleans, LA

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Background: Pasireotide is a novel multiligand somatostatin analogue that exhibits high binding affinity to 4 of 5 somatostatin receptor subtypes: sst_1,2,3 and sst₅. Compared with octreotide, pasireotide has 30, 5 and 40 times greater affinity for sst_1,3 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.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis

Abstract presentation from the 2006 ASCO Annual Meeting