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

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 - Drug Des Devel Ther (2015)

Bottom Line: Objective tumor response was a secondary outcome.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%).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.

View Article: PubMed Central - PubMed

Affiliation: Markey Cancer Center, University of Kentucky, Lexington, KY, USA.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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f2-dddt-9-5075: 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.

Mentions: One hundred ten patients were enrolled between April 2008 and April 2012, before the study was halted following a data monitoring committee recommendation due to a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (Figure 2). Baseline demographic and clinical characteristics of the patients in the two treatment arms were similar (Table 1).


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

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 - Drug Des Devel Ther (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562767&req=5

f2-dddt-9-5075: 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.
Mentions: One hundred ten patients were enrolled between April 2008 and April 2012, before the study was halted following a data monitoring committee recommendation due to a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (Figure 2). Baseline demographic and clinical characteristics of the patients in the two treatment arms were similar (Table 1).

Bottom Line: Objective tumor response was a secondary outcome.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%).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.

View Article: PubMed Central - PubMed

Affiliation: Markey Cancer Center, University of Kentucky, Lexington, KY, USA.

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.

No MeSH data available.


Related in: MedlinePlus