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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

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.
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f1-dddt-9-5075: 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.

Mentions: This was a multicenter, randomized, blinded, efficacy and safety, Phase III study of pasireotide LAR versus octreotide LAR in patients with metastatic NET of the digestive system who had inadequately controlled carcinoid symptoms. Planned enrollment was 216 patients (108 in each arm; see the “Sample size and interim analysis” section in supplementary materials, Table S1) from 47 centers in 15 countries (Argentina, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Norway, Poland, Singapore, Spain, Sweden, UK, and USA) (Figure 1; ClinicalTrials.gov identifier, NCT00690430).


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)

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.
© Copyright Policy
Related In: Results  -  Collection

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

f1-dddt-9-5075: 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.
Mentions: This was a multicenter, randomized, blinded, efficacy and safety, Phase III study of pasireotide LAR versus octreotide LAR in patients with metastatic NET of the digestive system who had inadequately controlled carcinoid symptoms. Planned enrollment was 216 patients (108 in each arm; see the “Sample size and interim analysis” section in supplementary materials, Table S1) from 47 centers in 15 countries (Argentina, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Norway, Poland, Singapore, Spain, Sweden, UK, and USA) (Figure 1; ClinicalTrials.gov identifier, NCT00690430).

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