Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Sep 3;9:5075-86.
doi: 10.2147/DDDT.S84177. eCollection 2015.

Phase III Study of Pasireotide Long-Acting Release in Patients With Metastatic Neuroendocrine Tumors and Carcinoid Symptoms Refractory to Available Somatostatin Analogues

Affiliations
Free PMC article
Clinical Trial

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 et al. Drug Des Devel Ther. .
Free PMC article

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.

Keywords: carcinoid syndrome; neuroendocrine tumors; pasireotide; progression-free survival; somatostatin analogues; symptom control.

Figures

Figure 1
Figure 1
Study design. Notes: aDiarrhea and/or flushing while receiving maximum approved doses of a currently available SSA for ≥3 months; bstratification groups (according to inadequately controlled baseline symptoms during a 2-week period [14 days] prior to randomization): D + F, mean daily bowel movements of four or more and total flushing episodes of five or more; D, mean daily bowel movements of four or more and total flushing episodes of less than five; F, mean daily bowel movements of less than four and total flushing episodes of 14 or more; cblinding was not maintained for patients who crossed over to pasireotide LAR. D, predominantly diarrhea group; D + F, diarrhea and flushing group; F, predominantly flushing group. Abbreviations: Octreotide LAR, octreotide long-acting repeatable; pasireotide LAR, pasireotide long-acting release; PS, performance status; RECIST, Response Evaluation Criteria In Solid Tumors; SSA, somatostatin analogues.
Figure 2
Figure 2
Patient disposition. Notes: Demographic and background characteristics. aTwo patients were incorrectly randomized; one patient randomized to the pasireotide LAR group actually received six injections of octreotide LAR (this patient crossed over to pasireotide LAR in the extension phase and received eight injections of pasireotide LAR), and one patient randomized to the octreotide LAR group actually received two injections of pasireotide LAR; bthree of four patients in the crossover group and one of two patients in the octreotide LAR group discontinued due to early study termination; cpatients who completed month 6 and did not enter the extension are not counted as discontinuations. Abbreviations: Octreotide LAR, octreotide long-acting repeatable; pasireotide LAR, pasireotide long-acting release.
Figure 3
Figure 3
Kaplan–Meier plot of progression-free survival based on investigator-assessed tumor response. Abbreviations: CI, confidence interval; n/N, number of responders/number of patients analyzed; octreotide LAR, octreotide long-acting repeatable; pasireotide LAR, pasireotide long-acting release; PFS, progression-free survival.

Similar articles

See all similar articles

Cited by 39 articles

See all "Cited by" articles

References

    1. Vinik AI, Woltering EA, Warner RR, et al. North American Neuroendocrine Tumor Society (NANETS) NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39(6):713–734. - PubMed
    1. Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–3072. - PubMed
    1. Klöppel G. Tumour biology and histopathology of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21(1):15–31. - PubMed
    1. National Cancer Institute . General Information about Gastrointestinal Carcinoid Tumors. NCI Web site; [Accessed August 25, 2014]. Available from: http://www.cancer.gov/cancertopics/pdq/treatment/gastrointestinalcarcinoid/HealthProfessional/page1#Section_231.
    1. National Comprehensive Cancer Network . Clinical practice Guideline in Oncology. Neuroendocrine Tumors Version 2. NCCN Web site; 2014. [Accessed August 25, 2014]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf.

Publication types

MeSH terms

Feedback