Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues

Edward M. Wolin, Barbara Jarzab, Barbro Eriksson, Thomas Walter, Christos Toumpanakis, Michael A. Morse, Paola Tomassetti, Matthias M. Weber, David R. Fogelman, John Ramage, Donald Poon, Brian Gadbaw, Jiang Li, Janice L. Pasieka, Abakar Mahamat, Fredrik Swahn, John Newell-Price, Wasat Mansoor, Kjell Öberg

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 – not reached) with pasireotide versus 6.8 months (5.6 – not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR.

Original languageEnglish (US)
Pages (from-to)5075-5086
Number of pages12
JournalDrug Design, Development and Therapy
Volume9
DOIs
StatePublished - Sep 2 2015

Keywords

  • Carcinoid syndrome
  • Neuroendocrine tumors
  • Pasireotide
  • Progression-free survival
  • Somatostatin analogues
  • Symptom control

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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  • Cite this

    Wolin, E. M., Jarzab, B., Eriksson, B., Walter, T., Toumpanakis, C., Morse, M. A., Tomassetti, P., Weber, M. M., Fogelman, D. R., Ramage, J., Poon, D., Gadbaw, B., Li, J., Pasieka, J. L., Mahamat, A., Swahn, F., Newell-Price, J., Mansoor, W., & Öberg, K. (2015). Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Design, Development and Therapy, 9, 5075-5086. https://doi.org/10.2147/DDDT.S84177