Switching patients with acromegaly from octreotide LAR to pasireotide LAR improves biochemical control: crossover extension to a randomized, double-blind, multicenter, Phase III study

Freda, Pamela U.; Fleseriu, Maria; van, der Lely A J; Colao, Annamaria; Sheppard, M. C.; Gu, Feng; Shen, Chiung‐Chyi; Gadelha, Mônica R.; Farrall, Andrew; Hermosillo, Resendiz Karina; Ruffin, Matthieu; Chen, YinMiao; Bronstein, Marcello D.

doi:10.1530/endoabs.32.p847

Cited by 4 publications

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“…Of the 81 patients who were inadequately controlled with octreotide LAR and switched to pasireotide LAR, 17.3% then achieved biochemical control 12 months after the crossover. On the other hand, none of the 38 patients who switched from pasireotide LAR to octreotide LAR experienced biochemical control 12 months after the crossover [42]. Tumor volume was reduced from the extension baseline by 24.7 and 17.9% in the patient populations crossed over to pasireotide LAR and octreotide LAR, respectively.…”

Section: Clinical Studiesmentioning

confidence: 99%

Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data

Samson¹

2015

Neuroendocrinology

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Background: Acromegaly is an insidious neuroendocrine disorder caused by hypersecretion of growth hormone (GH) by a somatotroph adenoma. Somatostatin receptor ligands (SRLs) are recommended as first-line medical therapy in patients for whom surgery has failed or is contraindicated. There are 5 known somatostatin receptor subtypes (SSTRs), 2 of which, i.e. SSTR2 and SSTR5, are expressed by a majority of somatotroph adenomas. The currently available SRLs, i.e. octreotide and lanreotide, primarily bind to SSTR2. Pasireotide (SOM230) is a new multireceptor-targeted SRL which has a broader binding profile and an increased affinity for SSTR1, 2, 3, and 5. Methods: PubMed searches were performed to identify all of the available published English language data on pasireotide with regard to the mechanism of action, in vitro effects, and clinical data. Results: Preclinical studies have demonstrated that pasireotide has a broader range of functional activity than octreotide. Recently, the efficacy of pasireotide in attenuating GH and insulin-like growth factor 1 (IGF-1) levels in patients with acromegaly has been evaluated in phase III clinical trials. Pasireotide demonstrated superiority over octreotide in achieving biochemical control (i.e. GH ≤2.5 µg/l and age- and sex-matched IGF-1 normalization) in patients with acromegaly, as well as significant efficacy in treating patients who were previously inadequately controlled on the maximum allowed doses of octreotide and lanreotide. Pasireotide-induced hyperglycemia was the most concerning adverse event but was reversible upon discontinuation of pasireotide. Conclusion: The clinical data support pasireotide as a promising new therapy for the treatment of acromegaly, and the long-acting formulation was recently approved in the US and Europe for the treatment of acromegaly.

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Section: Clinical Studiesmentioning

confidence: 99%

Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data

Samson¹

2015

Neuroendocrinology

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“…After a further 12 months' treatment (month 25), biochemical control was achieved in 14 (17 %) patients who switched to pasireotide, and no patients who switched to octreotide. From the time of treatment switch to month 25, tumour volume decreased by a mean of 24.7 % in the pasireotide group and 17.9 % in the octreotide group [24]. A reduction in tumour volume of [20 % throughout the same period was observed in 54.3 and 42.3 % of patients in each group, respectively.…”

Section: Extension Phasementioning

confidence: 90%

“…Among patients enrolled in the extension who had not achieved biochemical control at month 12 (n = 119), 81 switched from octreotide to pasireotide and 38 switched from pasireotide to octreotide at month 13 (results reported in an abstract and poster) [24]. After a further 12 months' treatment (month 25), biochemical control was achieved in 14 (17 %) patients who switched to pasireotide, and no patients who switched to octreotide.…”

Section: Extension Phasementioning

confidence: 99%

“…The hyperglycaemia associated with intramuscular pasireotide appears to be reversible when treatment is stopped, as evidenced in patients who switched from pasireotide to octreotide after 13 months of treatment (reported in an abstract and poster) [24]. Among these patients (n = 38), mean FPG and HbA 1c levels decreased from the time of treatment switch (127 mg/dL and 6.71 %, respectively) to month 3 (104 mg/dL and 6.15 %) and remained stable to month 12 (103 mg/dL and 6.0 %) [HbA 1c levels were estimated from a figure] [24].…”

Section: Patients Naive To Medical Therapymentioning

confidence: 99%

“…Among these patients (n = 38), mean FPG and HbA 1c levels decreased from the time of treatment switch (127 mg/dL and 6.71 %, respectively) to month 3 (104 mg/dL and 6.15 %) and remained stable to month 12 (103 mg/dL and 6.0 %) [HbA 1c levels were estimated from a figure] [24]. In contrast, among patients who switched from octreotide to pasireotide at month 13 (n = 81), mean FPG and HbA 1c levels increased from the time of treatment switch (104 mg/dL and 6.19 %), peaking at month 1 (FPG 141.4 mg/dL) and 3 (HbA 1c 7.0 %), then declining slightly and stabilizing to month 12 (125 mg/dL and 6.7 %, respectively).…”

Section: Patients Naive To Medical Therapymentioning

confidence: 99%

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Pasireotide in Acromegaly: A Review

McKeage

2015

Drugs

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Pasireotide (Signifor(®), Signifor(®) LAR) is a somatostatin analogue recently approved for the treatment of acromegaly. Unlike the first-generation agents, octreotide and lanreotide, which bind preferentially to somatostatin receptor (SSTR)-2, pasireotide binds to multiple SSTRs. This article reviews the clinical use and summarizes the pharmacological properties of intramuscular pasireotide in the treatment of acromegaly. The efficacy of pasireotide 40 mg every 28 days was superior to that of intramuscular octreotide 20 mg every 28 days with regard to biochemical control in a 12-month, phase III trial in medically naive patients. Similarly, in a 6-month, phase III trial in patients with acromegaly inadequately controlled with somatostatin analogues for at least 6 months, the efficacy of pasireotide 40 or 60 mg was superior to that of continued octreotide 30 mg or lanreotide autogel 120 mg (each drug was administered once every 28 days) with regard to biochemical control. The tolerability profile of intramuscular pasireotide is generally similar to that of first-generation agents, except for a higher incidence of hyperglycaemia-related adverse events with pasireotide. In clinical trials, the risk of developing pasireotide-associated hyperglycaemia was numerically greater in patients categorized as diabetic or prediabetic at baseline than in those with normal glucose tolerance. Careful monitoring of glycaemic status is required prior to and during pasireotide treatment and antidiabetic therapy should be commenced as indicated. Thus, in the treatment of acromegaly, pasireotide may be a more effective somatostatin analogue than other approved agents of the same class; however, the increased risk of hyperglycaemia needs to be considered and proactively managed.

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Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly

Silverstein

2016

Pituitary

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PurposeCushing’s disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia.MethodsClinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed.ResultsThe frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3–67.0 %) than in patients with CD treated with pasireotide SC (68.4–73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791–799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875–884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320–326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914–924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues.ConclusionsDisease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly. Hyperglycemic effects associated with pasireotide have a predictable pattern, can be managed with antidiabetic agents, and are reversible upon discontinuation.

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Switching patients with acromegaly from octreotide LAR to pasireotide LAR improves biochemical control: crossover extension to a randomized, double-blind, multicenter, Phase III study

Cited by 4 publications

References 1 publication

Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data

Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data

Pasireotide in Acromegaly: A Review

Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly

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