Octreotide Long-acting Release Research Articles

Somatostatin analogues as a treatment option for cystoid maculopathy in retinitis pigmentosa

AimsThis study aimed to evaluate the effectiveness of somatostatin analogues (SA) for cystoid maculopathy (CM) in retinitis pigmentosa (RP) patients.Materials and methodsIn this retrospective case series, clinical and imaging characteristics...

#2662 Octreotide-LAR in ADPKD patients with very low kidney function: a monocentric real-life experience

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, characterized by development of fluid-filled renal cysts leading to progressive expansion of kidney volume, with decline in kidney function up to end-stage renal disease (ESRD). Octreotide long-acting release (OCT-LAR) is a synthetic somatostatin analogue, which has been shown to reduce kidney and cysts growth and to slow the progression of kidney function decline in ADPKD patients. Although the evidence of the literature supporting the protective effect of the OCT-LAR against progression of the disease in ADPKD patients with both early and later-stages, to date no data are available in ADPKD patients treated with this somatostatin analogue in a real-world clinical setting. In August 2018 OCT-LAR was approved only in Italy for the treatment of ADPKD adult patients with eGFR ranging from 30 to 15 mL/min/1.73 m2 at elevated risk of progression towards ESRD. The present study is aimed to report for the first time the effects on renal function of OCT-LAR in ADPKD patients with severe renal insufficiency (stage 4 CKD) receiving this somatostatin analogue for therapeutic indication in a real-world clinical setting. Method We conducted a retrospective, ADPKD-population-based cohort study using healthcare data from the medical records of patients with ADPKD referred to the Department of Nephrology of University “Federico II” of Naples from November 2018 to April 2023 aimed to analyse within-patient clinical outcomes, including eGFR decline, before and after treatment with OCT-LAR. We include adult ADPKD patients (≥18 years) with GFR (eGFR) between 30 and 15 mL/min/1.73 m2, stably treated from at least 1 years with the regular dose of OCTR-LAR. The primary endpoint was the assessment of eGFR decline from 1 year before the start of the treatment (T-1) to baseline (T0), and after 1 year of therapy with OCT-LAR (T1) in the overall population and in two subgroups of patients with eGFR ≥ or < 25 ml/min/1.73 m2. Results 31 ADPKD patients were analysed (18 with eGFR ≥ 25 and 13 with eGFR < 25). Compared to pre-treatment period, eGFR decline significantly slowed during therapy with OCT-LAR in both eGFR groups (Table 1), while no difference was found between eGFR groups. After the first year of observation, 7 patients required dialysis (all with eGFR <25). Conclusion This is the first study reporting the effects of OCT-LAR on eGFR of ADPKD patients with advanced chronic kidney disease (CKD) in a real-world clinical setting. Our results suggest that, compared the last year of follow-up pre-treatment, OCT-LAR slows eGFR decline after 1 year.

Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Challenging diagnosis of resistance to thyroid hormone in a patient with COVID-19, pituitary microadenoma and unusual response to octreotide long-acting release test.

The resistance to thyroid hormone syndrome (RTHβ) occurs uncommonly and requires a high level of clinical suspicion and specific investigations to reach a precise diagnosis and to avoid unnecessary and potentially harmful therapies. We report a case of a young male patient referred to our unit for SARS-CoV-2 infection and atrial fibrillation with elevated thyroid hormones and non-suppressed thyroid-stimulating hormone (TSH), for which antithyroid therapy was prescribed. A mood disorder was reported in the medical history. The family history was unknown as the patient was adopted. Thyroid-specific antibodies were undetectable, and thyroid ultrasound revealed a normal thyroid gland without nodules. After the resolution of SARS-CoV-2 infection, the diagnostic workup continued, and the pituitary MRI revealed a small area ascribable to a microadenoma. Due to atrial fibrillation, the execution of the T3 test was contraindicated. The octreotide long-acting release (LAR) test showed an initial reduction of free thyroid hormones levels at first administration, which was consistent with the presence of a TSH-secreting pituitary tumour, although an escape from the response was observed after the following two injections of octreotide LAR. Indeed, the genetic investigation revealed a variant in heterozygosity of the THRβ gene (Pro453Ser), thus leading to an RTHβ diagnosis, and, therefore, medical treatment with triiodothyroacetic acid was initiated. After 2 years from the SARS-CoV-2 infection, the patient continues the follow-up at our outpatient clinic, and no other medical interventions are needed. RTHβ is a rare genetic syndrome characterised by discrepant thyroid function tests and by a dissociation between the observed hormone levels and the expected patient signs and symptoms. Features of thyroid hormone deficiency in TR-ß dependent tissues (pituitary gland, hypothalamus, liver and neurosensitive epithelia), as well as thyroid hormone excess in TR-α-dependent tissues (heart, bone, skeletal muscle and brain), may coexist in the same individual. Clinical pictures can be different even when the same variant occurs, suggesting that other genetic and/or epigenetic factors may play a role in determining the patient's phenotype. Differentiating RTHβ from a TSH-secreting pituitary tumour is very difficult, especially when a concomitant pituitary adenoma is detected during diagnostic workup. The injection of long-acting somatostatin analogues can help differentiate the two conditions, but it is important to detect any interference in the dosage of thyroid hormones to avoid an incorrect diagnosis. Genetic testing is fundamental to prevent unnecessary and potentially harmful therapies. Medical treatment with triiodothyroacetic acid was demonstrated to be effective in reducing thyroid hormone excess and controlling symptoms.

177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study.

LBA588 Background: Currently, there is no universally accepted first line (1L) therapy for higher grade, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and an unmet medical need remains in these patients (pts). Radioligand therapy (RLT) is an innovative cancer treatment that crosses the traditional domains of systemic, radiation or surgical therapies. The Phase 3 NETTER-2 study (NCT03972488) evaluated [177Lu]Lu-DOTA-TATE (hereafter 177Lu-DOTATATE) as 1L treatment in pts with Grade (G) 2 and G3 advanced GEP-NETs. This is the first trial to assess 1L RLT in any solid tumor. Methods: Eligible pts were newly diagnosed with somatostatin receptor-positive high G2 or G3 (Ki-67 ≥10% and ≤55%) advanced GEP-NETs within the last 6 months prior to enrollment. Pts were randomized (2:1) to receive 4 cycles of 177Lu-DOTATATE (4 × 7.4 GBq) plus 30 mg octreotide long-acting release (LAR) at 8-weekly intervals during 177Lu-DOTATATE treatment then every 4 weeks (177Lu-DOTATATE arm), or 60 mg octreotide LAR every 4 weeks (control arm), stratified by grade (G2 vs G3) and tumor origin (pancreas vs other). The primary endpoint was progression-free survival (PFS), centrally assessed using RECIST 1.1. Objective response rate (ORR), a key secondary endpoint, was tested hierarchically after PFS. Results: Overall, 226 pts were randomized to the 177Lu-DOTATATE (n = 151) or control (n = 75) arms. Most tumors originated in the pancreas (54.4%) or small intestine (29.2%); G3 tumors were reported in 35.0% of pts. Median cumulative dose of 177Lu-DOTATATE was 29.2 GBq, with 87.8% of pts receiving all 4 doses. Median PFS (95% confidence interval [CI]) was significantly prolonged by ~14.3 months from 8.5 months (7.7, 13.8) in the control arm to 22.8 months (19.4, not estimable) in the 177Lu-DOTATATE arm; stratified hazard ratio 0.276 (95% CI: 0.182, 0.418; p < 0.0001). The ORR was significantly higher in the 177Lu-DOTATATE arm (43.0%) vs the control arm (9.3%); stratified odds ratio 7.81 (95% CI: 3.32, 18.4; p < 0.0001). PFS and ORR results were consistent across all pre-specified demographic and prognostic subgroups. Among adverse events of special interest to RLT, G3/4 leukopenia, anemia and thrombocytopenia occurred in ≤3 pts each in the 177Lu-DOTATATE arm. One case of myelodysplastic syndrome was reported (177Lu-DOTATATE arm). Conclusion: 177Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, compared with high-dose octreotide LAR, in pts with newly diagnosed advanced G2 and G3 GEP-NETs. Safety was in line with the established profile of 177Lu-DOTATATE. This is the first randomized study to demonstrate efficacy of RLT as 1L treatment in any malignancy and will change clinical practice. Further investigations of RLT as a therapeutic option in other settings is warranted. Clinical trial information: NCT03972488 .

Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET

BackgroundThe current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG).MethodsSORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events.DiscussionThis is the first trial investigating the efficacy of CAM2029 versus SoC SRL therapy using a head-to-head, superiority trial design. It is expected to be the first trial to investigate the efficacy of increased dosing frequency of a high-exposure SRL. A BIRC will limit bias and measurement variability and ensure high-quality efficacy data. Additionally, inclusion of patients with well-differentiated Grade 3 NET may elucidate treatment strategies for this rarely investigated patient population.Trial registrationClinicalTrials.gov NCT05050942. Registered on 21st September 2021.

Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial

Background and aimsGastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We aimed to investigate the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. MethodsThe study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least four red blood cell (RBC) units and/or parental iron infusions in the year preceding randomization. Patients were allocated (1:1) to 40mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was one year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least one octreotide injection or followed standard of care for at least one month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. ResultsWe enrolled 62 patients (mean age 72 years, 32 males) from 17 Dutch hospitals in the octreotide (n=31) and standard of care (n=31) groups. Patients required a mean number of 20.3 (SD 15.6) transfusion units and 2.4 (SD 2.0) endoscopic procedures in the year before enrolment. The total number of transfusions was lower with octreotide (11.0; 95% CI, 5.5–16.5) compared to standard of care (21.2; 95% CI, 15.7–26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4–18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3–1.5). ConclusionOctreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. ClinicalTrials.gov, NCT02384122.

Treatment Patterns of Long-Acting Somatostatin Analogs for Neuroendocrine Tumors

Background: Long-acting somatostatin analog therapy (LA-SSA) is recommended as first-line therapy for treatment of unresectable or metastatic neuroendocrine tumors (NETs). Understanding treatment sequencing and dosing patterns of LA-SSA is essential for clinical decision-making to provide value-based management of NETs. Objective: To describe treatment patterns of LA-SSA among patients with NETs and subgroups with carcinoid syndrome (CS) in the United States. Methods: This retrospective study utilized claims data from MarketScan® databases to identify patients with NETs and newly treated with LA-SSA between January 1, 2015, and October 31, 2020. Patients were stratified by index LA-SSA (lanreotide and octreotide long-acting release [LAR]). Reported 28-day doses were based on claim fields for days’ supply/drug quantity or units of service. Dose escalation was defined as increases in quantity or frequency. Continuous variables, categorical variables, and Kaplan-Meier estimated treatment durations were compared using t-tests, chi-square/Fisher’s tests, and log-rank tests, respectively. Results: The study included 241 lanreotide and 521 octreotide LAR patients. Compared with octreotide LAR patients, treatment duration was longer for lanreotide patients (median, 41.3 vs 26.8 months; log-rank p=.004). Fewer lanreotide patients received rescue treatment with short-acting octreotide (7.9% vs 14.4%; p=.011), and a first (6.2% vs 27.3%) and second dose escalation (0.8% vs 5.2%; both p<.05). Among patients with doses reported, fewer lanreotide patients received above-label doses (2.5% [5/202] vs 14.4% [60/416]; p<.001). Among patients who ended treatment during follow-up, fewer lanreotide patients transitioned to another LA-SSA (18.9% [17/90] vs 33.6% [92/274]; p=.008). Similar treatment patterns were observed in CS subgroups. Results for switched treatment patterns were limited due to insufficient sample sizes. Discussion: Real-world treatment patterns of LA-SSA were assessed using more recent administrative claims data. Compared with octreotide LAR patients, lanreotide patients were more likely to remain longer on initial treatment and starting dose without dose escalations and less likely to use rescue treatment and transition to another LA-SSA after discontinuation of the index treatment. Conclusions: Findings from this claims study suggest a potential clinical benefit of lanreotide in NET management.

Treatment Patterns of Long-Acting Somatostatin Analogs for Neuroendocrine Tumors.

Background: Long-acting somatostatin analog therapy (LA-SSA) is recommended as first-line therapy for treatment of unresectable or metastatic neuroendocrine tumors (NETs). Understanding treatment sequencing and dosing patterns of LA-SSA is essential for clinical decision-making to provide value-based management of NETs. Objective: To describe treatment patterns of LA-SSA among patients with NETs and subgroups with carcinoid syndrome (CS) in the United States. Methods: This retrospective study utilized claims data from MarketScan® databases to identify patients with NETs and newly treated with LA-SSA between January 1, 2015, and October 31, 2020. Patients were stratified by index LA-SSA (lanreotide and octreotide long-acting release [LAR]). Reported 28-day doses were based on claim fields for days' supply/drug quantity or units of service. Dose escalation was defined as increases in quantity or frequency. Continuous variables, categorical variables, and Kaplan-Meier estimated treatment durations were compared using t-tests, chi-square/Fisher's tests, and log-rank tests, respectively. Results: The study included 241 lanreotide and 521 octreotide LAR patients. Compared with octreotide LAR patients, treatment duration was longer for lanreotide patients (median, 41.3 vs 26.8 months; log-rank p=.004). Fewer lanreotide patients received rescue treatment with short-acting octreotide (7.9% vs 14.4%; p=.011), and a first (6.2% vs 27.3%) and second dose escalation (0.8% vs 5.2%; both p<.05). Among patients with doses reported, fewer lanreotide patients received above-label doses (2.5% [5/202] vs 14.4% [60/416]; p<.001). Among patients who ended treatment during follow-up, fewer lanreotide patients transitioned to another LA-SSA (18.9% [17/90] vs 33.6% [92/274]; p=.008). Similar treatment patterns were observed in CS subgroups. Results for switched treatment patterns were limited due to insufficient sample sizes. Discussion: Real-world treatment patterns of LA-SSA were assessed using more recent administrative claims data. Compared with octreotide LAR patients, lanreotide patients were more likely to remain longer on initial treatment and starting dose without dose escalations and less likely to use rescue treatment and transition to another LA-SSA after discontinuation of the index treatment. Conclusions: Findings from this claims study suggest a potential clinical benefit of lanreotide in NET management.

THU061 Treatment Patterns In Acromegaly: Analysis Of Real-World US Insurance Claims From The MarketScan® Database

Abstract Disclosure: M. Fleseriu: Advisory Board Member; Self; Amryt, Ipsen, Recordati Rare Diseases, Pfizer, Inc. Grant Recipient; Self; Amryt, Crinetics, Ionis Pharmaceuticals Inc. A.L. Barkan: None. T.C. Brue: Advisory Board Member; Self; Advanz Pharma, Debio Pharm, Recordati Rare Diseases. Consulting Fee; Self; Ipsen, Recordati Rare Diseases, Novartis Pharmaceuticals, Pfizer, Inc. Grant Recipient; Self; Pfizer, Inc. Other; Self; Ipsen, Recordati Rare Diseases, Novartis Pharmaceuticals, Pfizer, Inc. E. Duquesne: Employee; Self; Ipsen. A. Houchard: Employee; Self; Ipsen. Stock Owner; Self; Ipsen. M. del Pilar Schneider: Employee; Self; Ipsen. A. Ribeiro-Oliveira Jr.: Employee; Self; Ipsen. Stock Owner; Self; Ipsen. S. Melmed: Advisory Board Member; Self; Ionis Pharmaceuticals Inc., Ipsen, Novo Nordisk, Recordati Rare Diseases. Grant Recipient; Self; Pfizer, Inc. Background: Medical treatment for acromegaly (characterized by excess growth hormone [GH] production) includes somatostatin receptor ligands (SRLs), dopamine agonists (DAs), and GH receptor antagonists (GHRAs). However, there are few real-world treatment evaluations in the US. We present treatment patterns for patients receiving medications for acromegaly (1/1/2010-7/31/2022). Methods: De-identified data were extracted from MarketScan®, a US health insurance claims database. Eligible patients: those receiving monotherapy or combination therapy (≥2 treatments overlapping for &amp;gt;3 months [m]) for ≥90 days without treatment gaps; ≥2 claims associated with acromegaly; data ≥3 m before and ≥6 m after diagnosis/first treatment claim (earlier date); and ≥18 years (y) old at diagnosis. Outcomes were: demographic characteristics; treatment frequency by line of treatment (LOT) and changes between LOTs (Sankey plot); treatment persistence for first LOT (LOT 1) monotherapies (Kaplan-Meier estimator); and treatment up-/downtitration (≥30% dose change, evaluated for octreotide long-acting release [OCT] and lanreotide depot [LAN]). Biochemical control values were unavailable in the database. Results: Of 882 patients, 50.1% were female; mean age at diagnosis was 48.6 y (standard deviation 13.6 y). In the cohort, 59.4% had exactly 1 LOT, 23.1% had exactly 2 LOTs, and 17.5% had exactly 3 LOTs. The most common LOT 1 medication class was first-generation SRLs: OCT (27.7%) and LAN (21.1%). Other LOT 1 classes were Das (cabergoline; 34.5%) and GHRAs (pegvisomant; 10.5%). Only 7 patients received second-generation SRL pasireotide and no patients received oral octreotide in LOT 1. Most patients initiated treatment with monotherapies (94.6%). In monotherapy LOT 1, GHRAs had the longest median persistence (pegvisomant; 24.8 m; 95% confidence interval [CI]: 16.59-32.49 m; n=93), followed by OCT and LAN (20.0 m; 95% CI: 16.98-23.87 m; n=430). Das had the shortest persistence (cabergoline; 14.4 m; 95% CI: 12.23-16.82 m; n=304). Among patients receiving OCT or LAN, 67.6% had ≥1 dose increase and 45.0% had ≥1 dose reduction. Conclusions: Despite guidelines recommending DA monotherapy for few select patients with acromegaly,1 our real-world analysis found that approximately one-third of patients initiated treatment with this class with the shortest treatment persistence. OCT and LAN monotherapies were also commonly used as LOT 1 and had longer persistence. GHRAs, the class with the longest persistence, were not common monotherapy in LOT 1, possibly because they do not target pituitary adenomas directly. Interestingly, only 5% of patients initiated treatment with combination therapies. Recommendations for individualized therapy2 should consider medication persistence and real-world treatment patterns. 1Giustina et al. Rev Endocr Metab Disord. 2020 2Fleseriu et al. Lancet Diabetes Endocrinol. 2022 Presentation: Thursday, June 15, 2023

THU070 Randomized, Placebo-controlled Phase 3 Trial Protocol Assessing The Efficacy And Safety Of Octreotide Subcutaneous Depot (CAM2029) In Patients With Acromegaly

Abstract Disclosure: D. Ferone: Advisory Board Member; Self; Recordati, Novartis-AAA, Sandoz, Camurus. Grant Recipient; Self; Bristol-Myers Squibb, Novartis-AAA, Ipsen, Camurus. Research Investigator; Self; Camurus. P. Freda: Research Investigator; Self; Camurus. L. Katznelson: Advisory Board Member; Self; Recordati, Camurus, Amryt. Research Investigator; Self; Camurus. F. Gatto: Research Investigator; Self; Camurus. A. Gilis-Januszewska: Research Investigator; Self; Camurus. M.B. Gordon: Advisory Board Member; Self; Camurus, Crinetics, HRA Pharma, Novo Nordisk, Recordati. Grant Recipient; Self; Amryt, Ascendis, Camurus, Corcept, Crinetics, Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Opko, Pfizer, Inc., Strongbridge. Research Investigator; Self; Camurus. P. Kadioglu: Research Investigator; Self; Camurus. P. Maffei: Research Investigator; Self; Camurus. J.R. Seufert: Research Investigator; Self; Camurus. J. Silverstein: Advisory Board Member; Self; Amryt, Recordati. Research Investigator; Self; Camurus. J.L. Spencer-Segal: Grant Recipient; Self; Camurus. Research Investigator; Self; Camurus. M. Harrie: Employee; Self; Camurus. A. Svedberg: Employee; Self; Camurus. F. Tiberg: Employee; Self; Camurus. Extended-release formulations of the somatostatin analogues (SSAs), octreotide and lanreotide, are first-line medical therapies for patients with acromegaly who have contraindications for, or are not cured by, surgical intervention and/or radiotherapy. Treatment goals, regardless of modality, include biochemical normalization of insulin-like growth factor 1 (IGF-1) and growth hormone (GH), symptom relief, tumor control, and maintenance of pituitary function. From the patient perspective, treatment satisfaction, autonomy, and quality of life may be as important as biochemical control. Constraints of current SSA formulations include incomplete biochemical and symptom control, and a lack of convenient self-administration options. Octreotide subcutaneous (SC) depot (CAM2029) is a novel FluidCrystal® formulation of octreotide designed for easy administration by patients, in a ready-to-use prefilled syringe or injection pen. In previous clinical trials, CAM2029 provided more than five-fold higher bioavailability compared to the currently marketed long-acting octreotide formulation.The efficacy and safety of CAM2029 in acromegaly is being evaluated in a 6-month, randomized, double-blind, placebo-controlled phase 3 trial (NCT04076462). 72 patients were randomized 2:1 to monthly SC doses of CAM2029 20 mg or placebo, with the option for self-administration. Key inclusion criteria included a biochemical and clinical diagnosis of acromegaly due to a pituitary adenoma with persistent or recurrent disease, treatment with a stable dose of octreotide long-acting release or lanreotide Autogel for at least 3 months as monotherapy, and controlled disease with IGF-1 ≤1 x upper limit of normal (ULN). Key exclusion criteria included GH ≥2.5 μg/L at screening, pituitary surgery within 6 months of screening, prior pituitary irradiation, and recent treatment with pasireotide, pegvisomant, or dopamine agonists. The primary endpoint is the proportion of patients with normalized IGF-1 (≤1 x ULN) after 6 months of treatment. Other endpoints include change from baseline of IGF-1, GH and patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication, Self-Injection Assessment Questionnaire, Acromegaly Quality of Life Questionnaire, EQ-5D-5L), safety and tolerability, clinical signs and symptoms of acromegaly, use of rescue medication and octreotide pharmacokinetics. The estimated primary completion date for the trial is May 2023. After completing study treatment, patients may switch to open-label treatment in a phase 3 long-term safety and extension trial of CAM2029 (NCT04125836). Presentation: Thursday, June 15, 2023

Treatment Patterns, Adherence, Persistence, and Health Care Resource Utilization in Acromegaly: A Real-World Analysis.

Treatment of acromegaly is multimodal for many patients, and medical treatments include somatostatin receptor ligands (SRLs), dopamine agonists (DAs), and growth hormone receptor antagonists (GHRAs). However, recent real-world evidence on treatment patterns for patients with acromegaly is limited. This study evaluated medication usage, treatment changes, adherence, persistence, comorbidities, and health care resource utilization using deidentified data from MarketScan, a US claims database. Eligible patients (n = 882) were those receiving monotherapy or combination therapy for ≥90 days without treatment gaps. Mean age at diagnosis was 48.6 years; 50.1% of patients were female. Over half (59.4%) had 1 line of treatment (LOT); 23.1% had 2 LOTs; 17.5% had at least 3 LOTs. Most patients (94.6%) initiated treatment with monotherapies. The most common first-line monotherapy treatments were cabergoline (DA, 36.8%), octreotide long-acting release (first-generation SRL, 29.5%), and lanreotide depot (first-generation SRL, 22.5%). Adherence for first-line treatments (proportion of days covered) was higher for first-generation SRLs (lanreotide depot: 0.8) compared with DAs (0.7). Treatment persistence (time between the first treatment record and a change in LOT/censoring) in LOT 1 was higher for GHRAs (24.8 months) and first-generation SRLs (20.0 months) compared with DAs (14.4 months). Female patients and those diagnosed at a younger age were more likely to have shorter treatment persistence. The most prevalent comorbidities were hyperlipidemia, essential hypertension, and sleep apnea. Patients with more comorbidities had more health care visits during the first year after diagnosis, suggesting increased disease burden. Real-world evidence on treatment patterns provides insights into recommendations for individualized therapy.

Bronchial Typical Carcinoid with Carcinoid Syndrome Successfully Treated with Everolimus and Octreotide: a Case Report

Background. Bronchopulmonary typical carcinoid tumors with distant metastasis and carcinoid syndrome are rare. Case. We report the case of a 77-year-old woman diagnosed with a bronchial typical carcinoid in the right middle lobe bronchus and multiple liver metastases. The patient presented with facial flushing and diarrhea, and the serotonin blood levels were elevated, indicative of carcinoid syndrome. Combination therapy with everolimus and octreotide maintained the patient in a healthy condition for approximately two years until she died in 2019. Conclusion. Bronchial typical carcinoids with multiple liver metastases and carcinoid syndrome in our patient was well-managed by combination therapy with everolimus and long-acting release octreotide.

Prescribing Characteristics of Octreotide Immediate-Release and Long-Acting Release in Patients with Neuroendocrine Tumors.

Treatment recommendations for patients with neuroendocrine tumors (NETs) include the use of octreotide long-acting release (LAR) for long-term therapy and immediate-release (IR) as rescue therapy to control the breakthrough symptoms of carcinoid syndrome (CS). High doses of LAR are commonly used in clinical practice. This study aimed to evaluate the real-world utilization of LAR and preceding IR use at the prescription and patient levels. We used an administrative claims database (2009-2018) containing privately insured enrollees. We calculated the normalized LAR dose from pharmacy claims and the initial mean IR daily dose at the prescription level. At the patient level, we conducted a retrospective cohort study that included patients continuously enrolled with ≥1 pharmacy claim of LAR and evaluated the frequency and the clinical reason for dose escalation of LAR. The definition of the above-label maximum dose of LAR was ≥30 mg/4 weeks. Nineteen percent of LAR prescriptions had an above-label maximum dose. Only 7% of LAR prescriptions had preceding IR use. There were 386 patients with NETs or CS vs. 570 with an unknown diagnosis. Comparing patients with NETs or CS to those with an unknown diagnosis, 22.3% vs. 11.0 % experienced dose escalations and 29.0% vs. 26.6% had IR use before dose escalation, respectively. LAR dose escalation occurred in 50.9% vs. 39.2% for symptom control, 12.3% vs. 7.1% for tumor progression control, and 16.6% vs. 6.0% for both reasons in NETs/CS and unknown groups, respectively. Octreotide LAR dosing above the label-maximum dose is common and IR rescue dosing appears to be underutilized.

Concurrent Targeting of Vasopressin Receptor 2 and Somatostatin Receptors in Autosomal Dominant Polycystic Kidney Disease: A Promising Approach for Autosomal Dominant Polycystic Kidney Disease Treatment?

1Division of Nephrology & Hypertension, Mayo Clinic College of Medicine and Science, Rochester, Minnesota 2Mayo Clinic Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic College of Medicine and Science, Rochester, Minnesota 3Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota 4Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine and Science, Rochester, Minnesota Correspondence: Dr. Marie C. Hogan, Mayo Clinic College of Medicine and Science, 200 1st St. SW, Rochester, MN 55905. Email: [email protected] See related article, “Effects of Octreotide–Long-Acting Release Added-on Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: Pilot, Randomized, Placebo-Controlled, Cross-Over Trial,” on pages 223–233.

Successful Treatment of Congenital Hyperinsulinism Due to KJNJ11 Gene Mutation with Long-Acting Release Octreotide: A Case Report from the Arab Region

AbstractCongenital hyperinsulinism is a rare hereditary condition that is caused by various gene mutations related to the function of the pancreatic β-cells. It is characterized by dysregulation of insulin secretion leading to profound and recurrent hypoglycemia. Its clinical presentation, histology, response to treatment, and underlying genetic defects are variable making it a heterogeneous condition. Pancreatectomy is indicated in diazoxide un-responsive cases. However, surgical treatment is associated with the possibility of persistent hypoglycemia and iatrogenic diabetes. We report a 3 months old girl who presented with hyperinsulinemic hypoglycemia. She was born to consanguineous parents and had a history of four neonatal deaths in siblings. Whole exome sequencing detected a KCNJ11 variant c.350_352del p.(Phe117del) in a homozygous state. Pancreatic scan (positron emission tomography/computed tomography) showed a diffusely increased radioisotope uptake in the head and tail of the pancreas. She was resistant to diazoxide and nifedipine and was shifted to octreotide treatment through multiple daily subcutaneous injections initially. Treatment was changed to monthly depot injection of octreotide that resulted in euglycemia. She kept a normal rate of growth, insulin-like growth factor-1, and liver function. This case is an example of an alternative effective medical therapy that avoids major surgical intervention and prevents long-term complication of recurrent hypoglycemia and iatrogenic diabetes resulting after surgery.

PRESTO 2: An International Survey to Evaluate Patients' Injection Experiences with the Latest Devices/Formulations of Long-Acting Somatostatin Analog Therapies for Neuroendocrine Tumors or Acromegaly.

Real-world data evaluating patients' injection experiences using the latest devices/formulations of the long-acting (LA) somatostatin analogs (SSAs) lanreotide Autogel/Depot (LAN; Somatuline®) and octreotide LA release (OCT; Sandostatin®) are limited. PRESTO 2 was a 2020/2021 e-survey comparing injection experience of adults with neuroendocrine tumors (NETs) or acromegaly treated with LAN prefilled syringe versus OCT syringe for > 3months in Canada, Ireland, the UK and the USA (planned sample size, 304). the proportion of patients with injection-site pain lasting > 2days after their most recent injection, analyzed using a multivariate logistic regression model. Secondary endpoints included interference with daily life due to injection-site pain and technical injection problems in patients with current SSA use for ≥ 6months. There were 304 respondents (acromegaly, n = 85; NETs, n = 219; LAN, n = 168; OCT, n = 136; 69.2% female; mean age, 59.6years). Fewer patients had injection-site pain lasting > 2days after the most recent injection with LAN (6.0%) than OCT (22.8%); the odds of pain lasting > 2days were significantly lower for LAN than OCT, adjusted for disease subgroup and occurrence of injection-site reactions (odds ratio [95% confidence interval]: 0.13 [0.06-0.30]; p < 0.0001). Injection-site pain interfered with daily life "a little bit" or "quite a bit" in 37.2% and 3.8% (LAN) versus 52.5% and 7.5% (OCT) of patients, respectively. Among patients with ≥ 6months' experience with current SSA (92.4% of patients), technical injection problems never occurred in 76.8% (LAN) and 42.9% (OCT) of patients. Compared with OCT, significantly fewer patients using LAN had injection-site pain lasting > 2days after their most recent injection. Also, fewer LAN-treated patients experienced technical problems during injection. These findings demonstrate the importance of injection modality for overall LA SSA injection experience for patients with acromegaly or NETs.

A systematic literature review to evaluate extended dosing intervals in the pharmacological management of acromegaly

PurposeThis systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness.MethodsMEDLINE/Embase/the Cochrane Library (2001–June 2021) and key congresses (2018–2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required.ResultsIn total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens.ConclusionsClinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control.

Octreotide Long-Acting Release and Everolimus for Recurrent Meningiomas

&#x0D; The systematic search resulted in 1 single-arm prospective study and 1 retrospective cohort study. No relevant randomized controlled trials, systematic reviews, or evidence-based guidelines were identified that met the criteria for this review.&#x0D; Evidence was limited, inconsistent, and of low quality for the clinical effectiveness of octreotide long-acting release in combination with everolimus in patients with recurrent meningiomas.&#x0D; The quantity and quality of current publications were not sufficient to draw a conclusion in support of or against the clinical effectiveness of octreotide long-acting release in combination with everolimus relative to other systematic therapies in patients with recurrent meningiomas.&#x0D; Additional research is required to inform decision-making in this context.&#x0D;

PMON66 A Systematic Literature Review to Evaluate Extended Dosing Intervals in the Pharmacological Management of Acromegaly

Abstract Background Acromegaly is a rare, lifelong disorder characterized by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Extended dosing intervals (EDIs) of pharmacological treatments may reduce patient burden and costs compared with standard dosing. This systematic literature review (SLR) investigated outcomes in patients with acromegaly receiving treatment at EDIs. Methods MEDLINE/Embase/the Cochrane Library (2001–June 2021) and key congresses (2018–2021) were searched for relevant literature; identified SLR bibliographies were also reviewed. A dual reviewer process was utilized. Included publications reported clinical effectiveness, safety, humanistic, and economic outcomes in longitudinal/cross-sectional studies in adult patients with acromegaly. Interventions included EDIs of lanreotide autogel (LAN), octreotide long-acting release (OCT), and pasireotide (all administered less often than every four weeks), oral octreotide (less than twice daily), pegvisomant (PEG; less than once daily), and cabergoline (less than twice weekly), with no comparator required. PROSPERO 2021: CRD42021278922. Results In total, 35 publications reported on 27 studies: 14 on PEG, 9 on LAN, and 4 on OCT as monotherapies or combination therapies at EDIs. No identified studies assessed EDIs of oral octreotide, pasireotide, or cabergoline. At Baseline, disease control and treatment history differed across studies. As compared with Baseline, treatment at EDIs resulted in reduced IGF-1 levels in 12/16 studies assessing LAN, OCT, or PEG (7–104 patients treated at EDIs) and GH levels in 5/6 studies (LAN/OCT; 15–32 patients). Normalized IGF-1 and/or GH, using study definitions, was achieved/maintained in 70%–100% of patients in 12/13 studies (LAN/OCT/PEG; 15–124 patients). Proportions of patients experiencing adverse events (n=4 studies reporting overall events; LAN/OCT/PEG; 8–96 patients) or discontinuing treatment (n=9; LAN/OCT/PEG; 7–124 patients) were similar across EDI and standard regimens. Health-related quality of life (HRQoL) improvement from Baseline was reported in 9/10 studies after treatment at EDIs (LAN/OCT/PEG; 7–109 patients); HRQoL did not deteriorate versus standard regimens. Patients preferred EDIs (2/2 studies; LAN/OCT; 8–112 patients), and satisfaction with EDIs was high (2/2 studies; LAN/OCT; 13–109 patients). Substantially reduced costs were observed with EDIs versus standard regimens in 3/3 studies (9–23 patients) with LAN (120 mg every 6 versus 4 weeks), OCT (20–30 mg every 6–12 versus 4 weeks), and PEG (40–160 mg weekly versus 15–60 mg daily, both with LAN/OCT). Conclusion Clinical, safety, and HRQoL outcomes in patients with acromegaly were similar and costs lower with EDIs versus standard regimens. Satisfaction was high with EDIs. Limitations, including variation in study design and endpoints, and small, heterogenous patient populations, precluded conducting meta-analyses. Physicians should consider EDIs where appropriate. Further clinical research may substantiate reduced patient and healthcare system burden with EDIs versus standard regimens. Study funded by Ipsen. Medical writing support provided by Costello Medical. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.