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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

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.
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f3-dddt-9-5075: 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.

Mentions: In a post hoc analysis, the median PFS based on investigator-assessed tumor response was 11.8 months (95% CI, 11.0 – not reached) in patients receiving pasireotide LAR versus 6.8 months (95% CI, 5.6 – not reached) in patients receiving octreotide LAR (unstratified Cox regression model HR, 0.46; 95% CI, 0.20–0.98; P=0.045) (Figure 3).


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)

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.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dddt-9-5075: 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.
Mentions: In a post hoc analysis, the median PFS based on investigator-assessed tumor response was 11.8 months (95% CI, 11.0 – not reached) in patients receiving pasireotide LAR versus 6.8 months (95% CI, 5.6 – not reached) in patients receiving octreotide LAR (unstratified Cox regression model HR, 0.46; 95% CI, 0.20–0.98; P=0.045) (Figure 3).

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