Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues.
Authors
Wolin, EJarzab, B
Eriksson, B
Walter, T
Toumpanakis, C
Morse, M
Tomassetti, P
Weber, M
Fogelman, D
Ramage, J
Poon, D
Gadbaw, B
Li, J
Pasieka, J
Mahamat, A
Swahn, F
Newell-Price, J
Mansoor, Was
Öberg, K
Affiliation
Markey Cancer Center, University of Kentucky, Lexington, KY, USAIssue Date
2015
Metadata
Show full item recordAbstract
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.Citation
Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. 2015, 9:5075-86 Drug Des Devel TherJournal
Drug design, Development and TherapyDOI
10.2147/DDDT.S84177PubMed ID
26366058Type
ArticleLanguage
enISSN
1177-8881ae974a485f413a2113503eed53cd6c53
10.2147/DDDT.S84177
Scopus Count
Collections
Related articles
- Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.
- Authors: Bronstein MD, Fleseriu M, Neggers S, Colao A, Sheppard M, Gu F, Shen CC, Gadelha M, Farrall AJ, Hermosillo Reséndiz K, Ruffin M, Chen Y, Freda P, Pasireotide C2305 Study Group
- Issue date: 2016 Apr 2
- Efficacy of octreotide long-acting repeatable in neuroendocrine tumors: RADIANT-2 placebo arm post hoc analysis.
- Authors: Strosberg JR, Yao JC, Bajetta E, Aout M, Bakker B, Hainsworth JD, Ruszniewski PB, Van Cutsem E, Öberg K, Pavel ME
- Issue date: 2015 Dec
- Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study.
- Authors: Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Öberg K, Van Cutsem E, Yao JC, RADIANT-2 Study Group
- Issue date: 2011 Dec 10
- Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors.
- Authors: Cives M, Kunz PL, Morse B, Coppola D, Schell MJ, Campos T, Nguyen PT, Nandoskar P, Khandelwal V, Strosberg JR
- Issue date: 2015 Feb
- Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study.
- Authors: Kvols LK, Oberg KE, O'Dorisio TM, Mohideen P, de Herder WW, Arnold R, Hu K, Zhang Y, Hughes G, Anthony L, Wiedenmann B
- Issue date: 2012 Oct