Pasireotide In Patients Research Articles

Efficacy and safety of pasireotide treatment in acromegaly: A systematic review and single arm meta-analysis.

Acromegaly is a rare chronic endocrine disorder associated with significant comorbidities. Many patients fail to achieve biochemical control with current medical therapies, including surgery and first-generation somatostatin ligands (fg-SRLs). We aimed to perform a systematic review and single-arm meta-analysis to evaluate the efficacy of the multi-receptor somatostatin ligand pasireotidein patients with active or uncontrolled acromegaly. We systematically searched PubMed, Embase, and Cochrane databases for studies that assessed the efficacy of pasireotide in patients withacromegaly and reported the outcomes of (1)biochemical control and its composite indicators; (2)normalized IGF-1 level and (3)low GH level.For the statistical analysis, we used R software. We included nine studies with a total of 590 patients: four clinical trials and five observational cohorts. 82.2% of the overall population consisted of inadequately controlled acromegaly patients. After a follow-up of 12months, the pooled biochemical control rate was 26.50% (95% CI 14.87-42.66). The prevalence of normalized IGF-1 and low GH levels was 36.27% (95% CI 29.15-43.39) and 34.76% (95% CI 24.58-44.95), respectively. Additionally, biochemical response rates were sustained throughout the extension phase of these studies. In a pooled analysis including four studies with extension phase results, the prevalence of biochemical control rate was 29.03% (95% CI 11.49-46.58) with 76 events out of 281 patients. The most commonly reported adverse events were gastrointestinal disturbances in 31.26% (95% CI 7.44-72.01) and hyperglycemia in 29.55% (95% CI 21.80-37.29) of patients. The incidence of new-onset diabetes mellitus significantly increased after pasireotide treatment, with a rate of 23.36% (95% CI 19.58-27.13). Pasireotide demonstrates biochemical control in patients with active or uncontrolled acromegaly. Although a high rate of hyperglycemic adverse events and diabetes mellitus related to the treatment were observed, most of them were manageable.

Long-term safety and efficacy of subcutaneous pasireotide in patients with cushing's disease: results from a non-interventional study

Long-term safety and efficacy of subcutaneous pasireotide in patients with cushing's disease: results from a non-interventional study

Long-term Efficacy and Safety of Pasireotide in Patients With Acromegaly: 14 Years of Single-Center Real-World Experience.

Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control. As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed. A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal). Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment. Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR.

Pasireotide is a second-generation somatostatin receptor ligand (SRL) used for treating acromegaly. Its clinical use is limited by adverse effects on glucose homeostasis. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity associated with pasireotide in patients not controlled by first-generation SRLs. We performed a retrospective study. The efficacy (growth hormone (GH)/insulin-like growth factor (IGF-1) concentrations; tumor size) and effect on glucose homeostasis were analyzed in 33 patients. Longitudinal data on oral glucose tolerance tests were available before, shortly (mean ± s.d., 6.1 ± 3.8 months) and long term (24.4 ± 11.1 months) after initiation of pasireotide in 14 patients. Insulin secretion (insulinogenic index; disposition index) and insulin sensitivity were calculated by validated indices. Pasireotide-induced diabetes occurred in 12 patients (36%). It was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term (insulinogenic index, median (min; max), 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; P = 0.028; disposition index, 1.45 (0.42; 4.88) vs 0.53 (0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; P = 0.024). No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for antidiabetic treatment. Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of antidiabetic treatment for pasireotide-induced hyperglycemia. Pasireotide, a second-generation SRL used for treating acromegaly, may be associated with glucose metabolism impairment. In a retrospective study of 33 patients, we observed that treatment with pasireotide was associated with normalization of serum IGF-1 in almost 60% of patients, but one-third of patients developed diabetes. In the patients who stopped pasireotide because of hyperglycemia, HbA1c promptly decreased. Longitudinal data in 14 patients show that diabetes is mediated by impaired insulin secretion, which occurred shortly and then remained stable on long term, while no significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia.

Long-term efficacy and safety of pasireotide in patients with Cushing's disease: a monocentric experience

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Gender-Specific Efficacy Revealed by Head-to-Head Comparison of Pasireotide and Octreotide in a Representative In Vivo Model of Nonfunctioning Pituitary Tumors.

Simple SummaryNo effective medical therapy exists for residual/recurrent nonfunctioning pituitary tumors (NFPTs). First-generation somatostatin analogs (SSAs) like octreotide targeting somatostatin receptor type 2 (SSTR2) are the mainstay therapy for functioning PTs, but have shown little effect in NFPTs. This is in agreement with an SSTR profile characterized by low SSTR2, and high SSTR3 levels in the latter. Pasireotide a multi-SSTR-preferring SSA, should be effective against NFPTs. To test this hypothesis, we conducted a head-to-head comparison of octreotide and pasireotide in the only spontaneous in vivo model of NFPTs (MENX rats), which recapitulates the human disease. Pasireotide showed a superior anti-tumor effect vs. octreotide, especially in females. Interestingly, Sstr3 levels were higher in female vs. male NFPTs. A sex-related SSTR3 expression may extend to human NFPTs, thereby representing a tool for patient stratification. Our results have translational relevance for the medical treatment of patients with residual/recurrent NFPTs currently lacking efficacious therapeutic options.Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors’ proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal Sstr3 expression was significantly higher in the former group. It is noteworthy that female human NFPTs patients also have a trend towards higher SSTR3 expression. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.

Pasireotide administration after pancreaticoduodenectomy may decrease clinically relevant postoperative pancreatic fistula in high-risk patients with small pancreatic ducts, soft pancreatic parenchyma and cystic or neuroendocrine neoplasia

ObjectivesPost-operative pancreatic fistula (POPF) is a feared complication after a pancreaticoduodenectomy. Previously in a randomized trial found fewer clinically relevant fistulas (CR-POPF) accompanying administration of perioperative pasireotide. Our hospital previously found that the risk for CR-POPF reached 7% in pancreaticoduodenectomy patients. Here, we aimed to determine the CR-POPF rate accompanying prophylactic pasireotide in patients with a normal pancreas at resection level. MethodsIn this clinical study, perioperative pasireotide was administered to pancreaticoduodenectomy patients treated between 1 July 2014 and 30 April 2016. High-risk individuals were defined preoperatively by the surgeon based on the following: no dilatation of the pancreatic duct, suspected soft pancreas and a cystic or neuroendocrine tumor at the head of the pancreas. If the pancreas was considered hard at surgery, thereby carrying a lower risk for fistula, pasireotide was discontinued following one preoperative 900-μg dose. Among high-risk patients, pasireotide was continued for one week or until discharge from the hospital. ResultsDuring the study period, 153/215 pancreatic operations were pancreaticoduodenectomies, 58 (38%) of which were considered high risk for developing clinically significant pancreatic fistula. Among these, 4 (2.6%) developed a grade B or C fistula: 2 in the pasireotide group [3.5%, 95% confidence interval (CI) 0.4–11.9%], 1 in the low-risk group (1.2%, 95% CI 0.0–6.4%; difference: 2.3%, 95% CI -6.4–17.3%) and 1 in the discontinued group (10%). ConclusionWe found similar rates of CR-POPF among high- and low-risk patients undergoing pancreaticoduodenectomy when using prophylactic perioperative pasireotide in high-risk patients.

Effect of Hydrocortisone vs Pasireotide on Pancreatic Surgery Complications in Patients With High Risk of Pancreatic Fistula

Both hydrocortisone and pasireotide have been shown in randomized clinical trials to be effective in reducing postoperative complications of pancreatic surgery, but to date no randomized clinical trial has evaluated the effectiveness of pasireotide compared with hydrocortisone. To assess the noninferiority of hydrocortisone compared with pasireotide in reducing complications after partial pancreatectomy. A noninferiority, parallel-group, individually randomized clinical trial was conducted at a single academic center between May 19, 2016, and December 17, 2018. Outcome collectors and analyzers were blinded. A total of 281 patients undergoing partial pancreatectomy were assessed for inclusion. Patients younger than 18 years, those allergic to hydrocortisone or pasireotide, patients undergoing pancreaticoduodenectomy with hard pancreas or dilated pancreatic duct, and patients not eventually undergoing partial pancreatectomy were excluded. Modified intention-to-treat analysis was used in determination of the results. Treatment included pasireotide, 900 μg, subcutaneously twice a day for 7 days or hydrocortisone, 100 mg, intravenously 3 times a day for 3 days. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days. The noninferiority limit was set to 9 CCI points. Of the 281 patients (mean [SD] age, 63.8 years) assessed for eligibility, 168 patients (mean [SD] age, 63.6 years) were randomized and 126 were included in the modified intention-to-treat analyses. Sixty-three patients received pasireotide (35 men [56%]; median [interquartile range] age, 64 [56-70] years) and 63 patients received hydrocortisone (25 men [40%]; median [interquartile range] age, 67 [56-73] years). The mean (SD) CCI score was 23.94 (17.06) in the pasireotide group and 30.11 (20.47) in the hydrocortisone group (mean difference, -6.16; 2-sided 90% CI, -11.73 to -0.60), indicating that hydrocortisone was not noninferior. Postoperative pancreatic fistula was detected in 34 patients (54%) in the pasireotide group and 39 patients (62%) in the hydrocortisone group (odds ratio, 1.39; 95% CI, 0.68-2.82; P = .37). One patient in the pasireotide group and 2 patients in the hydrocortisone group died within 30 days. In subgroup analyses of patients undergoing distal pancreatectomy, the CCI score was a mean of 10.3 points lower (mean [SD], 16.03 [11.94] vs 26.28 [21.76]; 2-sided 95% CI, -19.34 to -2.12; P = .03) and postoperative pancreatic fistula rate was lower (37% vs 67%; P = .02) in the pasireotide group compared with the hydrocortisone group. In this study, hydrocortisone was not noninferior compared with pasireotide in patients undergoing partial pancreatectomy. Pasireotide may be more effective than hydrocortisone in patients undergoing distal pancreatectomy. ClinicalTrials.gov identifier: NCT02775227; EudraCT identifier: 2016-000212-16.

Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs.

Introduction: Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I. Outcomes from a Phase IIIb open-label study of patients with uncontrolled acromegaly on first-generation SSAs switching to pasireotide are reported.Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 μg/L from a five-point profile over 2 h, and IGF-I >1.3× upper limit of normal [ULN]) despite ≥3 months' treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be increased (maximum: 60 mg/28 days) after week 12 if biochemical control was not achieved, or decreased (minimum: 10 mg/28 days) for tolerability. Patients who completed 36 weeks' treatment could continue receiving pasireotide during an extension (weeks 36–72) when concomitant medication for acromegaly was permitted. Primary endpoint was proportion of patients with mGH <1 μg/L and IGF-I <ULN at week 36. Biochemical control was also assessed during the extension. Safety was assessed throughout.Results: One hundred and twenty-three patients were enrolled and received pasireotide; 88 patients continued into the extension. Overall, 18 [14.6% (95% CI: 8.9–22.1)] patients achieved mGH <1 μg/L and IGF-I <ULN at week 36; biochemical control was achieved in 42.9% with screening mGH 1.0–2.5 μg/L and 6.4% with screening mGH >2.5 μg/L. For patients who entered the extension, 14.8% (95% CI: 8.1–23.9), 12.5% (95% CI: 6.4–21.3), 14.8% (95% CI: 8.1–23.9) and 11.4% (95% CI: 5.6–19.9) had mGH <1 μg/L and IGF-I <ULN at weeks 36, 48, 60, and 72, respectively. During the overall study period, most frequent investigator-reported drug-related adverse events were hyperglycemia (41.5%), diabetes mellitus (23.6%), and diarrhea (11.4%).Conclusions: Switching to long-acting pasireotide provided biochemical control in some patients, which was sustained with continued treatment. Long-term safety and tolerability of long-acting pasireotide was consistent with the known safety profile. These data support long-acting pasireotide for some patients with acromegaly who are uncontrolled on first generation SSAs.Clinical Trial Registration: clinicaltrials.gov, identifier: NCT02354508.

Stereotactic Body Radiotherapy for locally advanced pancreatic cancer

Post-operative pancreatic fistula (POPF) is a feared complication after a pancreaticoduodenectomy. Previously in a randomized trial found fewer clinically relevant fistulas (CR-POPF) accompanying administration of perioperative pasireotide. Our hospital previously found that the risk for CR-POPF reached 7% in pancreaticoduodenectomy patients. Here, we aimed to determine the CR-POPF rate accompanying prophylactic pasireotide in patients with a normal pancreas at resection level.In this clinical study, perioperative pasireotide was administered to pancreaticoduodenectomy patients treated between 1 July 2014 and 30 April 2016. High-risk individuals were defined preoperatively by the surgeon based on the following: no dilatation of the pancreatic duct, suspected soft pancreas and a cystic or neuroendocrine tumor at the head of the pancreas. If the pancreas was considered hard at surgery, thereby carrying a lower risk for fistula, pasireotide was discontinued following one preoperative 900-μg dose. Among high-risk patients, pasireotide was continued for one week or until discharge from the hospital.During the study period, 153/215 pancreatic operations were pancreaticoduodenectomies, 58 (38%) of which were considered high risk for developing clinically significant pancreatic fistula. Among these, 4 (2.6%) developed a grade B or C fistula: 2 in the pasireotide group [3.5%, 95% confidence interval (CI) 0.4–11.9%], 1 in the low-risk group (1.2%, 95% CI 0.0–6.4%; difference: 2.3%, 95% CI -6.4–17.3%) and 1 in the discontinued group (10%).We found similar rates of CR-POPF among high- and low-risk patients undergoing pancreaticoduodenectomy when using prophylactic perioperative pasireotide in high-risk patients.

Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing\u2019s disease: interim results from a long-term real-world evidence study

PurposeClinical trials have demonstrated the favorable efficacy/safety profile of pasireotide in patients with Cushing’s disease (CD). We report interim long-term results of an ongoing real-world evidence study of subcutaneous pasireotide in patients with CD.MethodsAdults with CD receiving pasireotide, initiated before (prior-use) or at study entry (new-use), were monitored for ≤ 3 years during a multicenter observational study (http://clinicaltrials.gov identifier NCT02310269). Primary objective was to assess long-term safety of pasireotide alone or with other CD therapies.ResultsAt the time of this interim analysis, 127 patients had received pasireotide (new-use, n = 31; prior-use, n = 96). Eight patients had completed the 3-year observation period, 53 were ongoing, and 66 had discontinued. Among 31 new-use and 92 prior-use patients with ≥ 1 safety assessment, respectively: 24 (77%) and 37 (40%) had drug-related adverse events (AEs); 7 (23%) and 10 (11%) had serious drug-related AEs. Most common drug-related AEs were nausea (14%), hyperglycemia (11%) and diarrhea (11%); these were more frequently reported in new users and mostly of mild-to-moderate severity. 14 (45%) new-use and 15 (16%) prior-use patients experienced hyperglycemia-related AEs. Mean urinary free cortisol (mUFC) was within normal range at baseline and months 1, 12 and 24, respectively, in: 1/16 (6%), 9/18 (50%), 1/3 (33%) and 0/0 new users; 28/43 (65%), 15/27 (56%), 27/33 (82%) and 12/19 (63%) prior users.ConclusionsPasireotide is well tolerated and provides sustained reductions in mUFC during real-world treatment of CD. The lower rate of hyperglycemia-related AEs in prior users suggests that hyperglycemia tends not to deteriorate if effectively managed soon after onset.Clinical Trial Registration Number: NCT02310269.

Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, Expanded-Access Study.

Introduction: The efficacy and safety of subcutaneous (sc) pasireotide have been evaluated in a Phase III trial. Here, we report safety and efficacy results from a multinational, expanded-access study of pasireotide sc in patients with Cushing's disease (CD) in a real-world setting (clinicaltrials.gov, identifier: NCT01582061).Methods: Adults with active CD previously untreated with pasireotide were enrolled; pasireotide sc was initiated at 600 μg twice daily (bid; EU countries) or 900 μg bid (non-EU countries; 600 μg bid in patients with impaired glucose metabolism). Pasireotide dose could be adjusted in 300 μg increments/decrements to a maximum of 900 μg bid or minimum of 300 μg bid for sustained urinary free cortisol (UFC) normalization/tolerability issues. Primary objective: document the safety of pasireotide sc in patients with CD. Key secondary objectives: assess the proportion of patients with mean UFC (mUFC) not exceeding the upper limit of normal (ULN) and changes from baseline in clinical signs/symptoms and quality of life (QoL) to weeks 12, 24, and 48.Results: One hundred and four patients received pasireotide: female, n = 84 (80.8%); median duration of pasireotide exposure, 25.1 weeks; median (range) baseline mUFC, 321.2 nmol/24 h (142–10,920; 2.3 × ULN [1.0–79.2]). Forty (38.5%) patients completed the study. The most common reasons for premature discontinuation of pasireotide were unsatisfactory therapeutic effect (n = 26, 25.0%) and adverse events (AEs; n = 20, 19.2%). Drug-related grade 3/4 AEs or drug-related serious AEs (primary endpoint) were documented in 42 (40.4%) patients, most commonly diabetes mellitus (n = 12, 11.5%) and hyperglycemia (n = 8, 7.7%). All patients experienced ≥1 AE and most (n = 102; 98.1%) reported ≥1 drug-related AE; six (5.8%) patients discontinued treatment because of hyperglycemia-related AEs. At weeks 12, 24, and 48, respectively, 36/66 (54.5%), 22/46 (47.8%), and 9/21 (42.9%) evaluable patients had normalized mUFC levels. Clinical signs/symptoms and QoL were also improved.Conclusions: In an international, real-world, clinical-practice setting, pasireotide sc was generally well-tolerated (no new safety signals were identified), effectively reduced UFC (normalization in ~50% of evaluable patients) and improved clinical signs and QoL in patients with CD. While hyperglycemia-related AEs were common, consistent with previous studies, most were manageable, with <6% of patients discontinuing treatment because of these events.

Biochemical control was sustained with long-acting pasireotide in patients with uncontrolled acromegaly over continued treatment with first-generation somatostatin analogues (SSAs): Results from the extension of phase 3b, open-label study

Biochemical control was sustained with long-acting pasireotide in patients with uncontrolled acromegaly over continued treatment with first-generation somatostatin analogues (SSAs): Results from the extension of phase 3b, open-label study

The role of pasireotide in developing clinically significant pancreatic fistula

Background: Pancreatic surgery has a high rate of morbidity mainly associated with a clinically significant pancreatic fistula types b and c (CSPF). A randomized study showed a reduction in the development of CSPF with the use of pasireotide. The aim of this study is to evaluate the role of pasireotide in patients undergoing pancreatic surgery, to identify factors associated with a CSPF. Methods: A retrospective analysis of our prospectively collected data base of pancreatic surgery between 2013 and 2018 was performed. Patients with total pancreatectomy were excluded from the analysis. Included patients were divided into Group A (treated with 0.9 mg subcutaneous pasireotide BID) and Group B (without pasireotide). Clavien-Dindo classification was used to assess 90-day perioperative morbidity. The incidence and factors associated with the development of a CSPF were evaluated using uni and multi-variate analysis in Stata 14 (StataCorp, TX). Results: During the analyzed 132 patients were operated on 74 women (56%) with a median age of 59 (16 - 87). The main diagnoses were ductal adenocarcinoma (n = 27) and neuroendocrine tumor (n = 24). 79 patients had a PDD (60%). Grade ≥ 3 morbidity occurred in 40 (30%) of then; Group A n: 16 (22%) vs group B n: 24 (41%). Type b-c fistula were presented in 18 patients (13,6%), group A n: 7 (10%) vs group B: 11 (19%) (p = 0.20). The wirsung size of less than 4 mm was related to the presence of type b y c fistula (p = 0.03). Patients with soft pancreas had less incidence of CSPF 3 (9%) in Group A vs 8 (16%) in Group B (p = 0.49). No relation was found between the nutritional status and the development of fistulas (p = 0.38). 90 days mortality was 3%. A multivariate analysis did not show any significant factor associated with CSPF, except the wirsung size. Conclusion: The use of pasireotide was associated with decreasing the risk of CSPF and a lower rate of grade ≥ 3 complications. However, this affirmation was not significant probably by the non number of patients evaluated.

Does giving pasireotide to patients undergoing pancreaticoduodenectomy always pay for itself?

Previous cost evaluation studies reported either no increase or cost-saving using pasireotide in patients undergoing pancreaticoduodenectomy. We examined the likelihood and magnitude of cost-saving when using pasireotide at our institution to determine the generalizability of prior reports. Cost data were obtained for a cohort of 440 patients undergoing pancreaticoduodenectomy at a single institution during 2009–2016. A statistical model was used to simulate the cost of patient care had they received pasireotide. Sensitivity analyses were performed to assess the impact of pasireotide price and pancreatic fistula rate on cost. With a fistula rate of 10.2% and a current price for pasireotide of $1257, the likelihood of cost-saving is 60%. When cost-saving does occur, the mean cost-saving per patient is $1442, 2.5–97.5% quantile difference (QD): $69–3756. At the same pasireotide price but with a fistula rate of 30%, the likelihood of cost-saving increases to 91% with a mean cost-saving of $4030, 2.5–97.5% QD: $402–8511. At the same fistula rate but with a pasireotide price of $1000, the likelihood of cost-saving increases to 65% with a cost-saving of $1566, 2.5–97.5% QD: $75–3979. At its current price, and with the fistula rate at our institution, pasireotide is more likely to pay for itself than not, but there is a significant probability that it will not be cost-saving. Negotiating a better price (i.e., to the lowest found in the literature) will reduce the likelihood of pasireotide not being cost-saving by 5%.

A prospective study of pasireotide in patients undergoing pancreaticoduodenectomy: a propensity score matched analysis

A prospective study of pasireotide in patients undergoing pancreaticoduodenectomy: a propensity score matched analysis

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma

IntroductionSomatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT metastatic melanoma.Patients and methodsPatients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months. Primary endpoint was safety in the first 8 weeks of dose-escalation phase.ResultsThe study was terminated early due to slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four reached the high dose level: two patients reached 3600 µg in dose-escalation and follow-up phases and two patients reached 3600 µg in dose-escalation and long-acting pasireotide 80 mg in follow-up phases and were stable for >5 months. Most common adverse events (AEs) during dose-escalation phase in ≥2 patients (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study drug-related AEs were diarrhoea and nausea, reported in one patient. Partial response was documented in one patient and stable disease in another.ConclusionsPasireotide was well tolerated, and safety results were similar to those previously reported in other indications. Further studies are needed to evaluate its antitumour activity alone and in combination with other drugs in melanoma.

Late-night salivary cortisol (LNSC) levels in a Phase III study of long-acting pasireotide in patients with Cushing's disease (CD)

Late-night salivary cortisol (LNSC) levels in a Phase III study of long-acting pasireotide in patients with Cushing's disease (CD)

Long-term efficacy and safety of once-monthly pasireotide in patients with Cushing's disease: A Phase III extension study

Long-term efficacy and safety of once-monthly pasireotide in patients with Cushing's disease: A Phase III extension study

Predictors of response to long-acting pasireotide in patients with Cushing's disease during a Phase III study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)