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

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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
Externally publishedYes

Fingerprint

Octreotide
Neuroendocrine Tumors
Carcinoid Tumor
Somatostatin
Confidence Intervals
Disease-Free Survival
Clinical Trials Data Monitoring Committees
Odds Ratio
pasireotide
Neoplasms
Drug-Related Side Effects and Adverse Reactions
Hyperglycemia
Nausea
Fatigue
Gastrointestinal Tract

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. / Wolin, Edward M.; Jarzab, Barbara; Eriksson, Barbro; Walter, Thomas; Toumpanakis, Christos; Morse, Michael A.; Tomassetti, Paola; Weber, Matthias M.; Fogelman, David R.; Ramage, John; Poon, Donald; Gadbaw, Brian; Li, Jiang; Pasieka, Janice L.; Mahamat, Abakar; Swahn, Fredrik; Newell-Price, John; Mansoor, Wasat; Öberg, Kjell.

In: Drug Design, Development and Therapy, Vol. 9, 02.09.2015, p. 5075-5086.

Research output: Contribution to journalArticle

Wolin, EM, Jarzab, B, Eriksson, B, Walter, T, Toumpanakis, C, Morse, MA, Tomassetti, P, Weber, MM, Fogelman, DR, Ramage, J, Poon, D, Gadbaw, B, Li, J, Pasieka, JL, 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, vol. 9, pp. 5075-5086. https://doi.org/10.2147/DDDT.S84177
Wolin, Edward M. ; Jarzab, Barbara ; Eriksson, Barbro ; Walter, Thomas ; Toumpanakis, Christos ; Morse, Michael A. ; Tomassetti, Paola ; Weber, Matthias M. ; Fogelman, David R. ; Ramage, John ; Poon, Donald ; Gadbaw, Brian ; Li, Jiang ; Pasieka, Janice L. ; Mahamat, Abakar ; Swahn, Fredrik ; Newell-Price, John ; Mansoor, Wasat ; Öberg, Kjell. / Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. In: Drug Design, Development and Therapy. 2015 ; Vol. 9. pp. 5075-5086.
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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.",
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AU - Jarzab, Barbara

AU - Eriksson, Barbro

AU - Walter, Thomas

AU - Toumpanakis, Christos

AU - Morse, Michael A.

AU - Tomassetti, Paola

AU - Weber, Matthias M.

AU - Fogelman, David R.

AU - Ramage, John

AU - Poon, Donald

AU - Gadbaw, Brian

AU - Li, Jiang

AU - Pasieka, Janice L.

AU - Mahamat, Abakar

AU - Swahn, Fredrik

AU - Newell-Price, John

AU - Mansoor, Wasat

AU - Öberg, Kjell

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N2 - 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.

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KW - Neuroendocrine tumors

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KW - Progression-free survival

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