LANREOTIDE THERAPY IN CARCINOID SYNDROME: PROSPECTIVE ANALYSIS OF PATIENT-REPORTED SYMPTOMS IN PATIENTS RESPONSIVE TO PRIOR OCTREOTIDE THERAPY AND PATIENTS NAÏVE TO SOMATOSTATIN ANALOGUE THERAPY IN THE ELECT PHASE 3 STUDY.

OBJECTIVE: This ELECT prospective analysis examined lanreotide depot/autogel for carcinoid syndrome (CS) symptom control in patients with neuroendocrine tumors (NETs) who were responsive to prior octreotide (prior octreotide group) compared with patients who were naïve to prior somatostatin analogue treatment (de novo group). METHODS: Adults with histopathologically confirmed NET and stable CS (diarrhea and/or flushing) were randomized to subcutaneous (SC) lanreotide 120 mg or placebo every 4 weeks for 16 weeks. Patients reported diarrhea and/or flushing symptom severity and frequency and short-acting SC octreotide rescue therapy daily using an Interactive Voice/Web Response System. To evaluate the efficacy of lanreotide compared with placebo, the novel primary endpoint of patient-determined use of SC octreotide rescue therapy for breakthrough symptoms was used as a surrogate for symptom control. Clinically meaningful patient-reported treatment benefit was examined using daily patient-reported symptoms of diarrhea and flushing. RESULTS: Of the 115 randomized patients, 51 (n = 26 lanreotide, n = 25 placebo) were octreotide-naïve (de novo) and 64 (n = 33 lanreotide; n = 31 placebo) received prior octreotide. Lanreotide versus placebo patients had a lower mean percentage of days of SC octreotide rescue therapy in de novo and prior octreotide groups (least squares [LS] mean difference -19.1, P = .0477 and -6.9, P = .4332, respectively). The mean percentage of days with moderate/severe diarrhea and/or flushing was lower in lanreotide versus placebo patients in de novo and prior octreotide groups (LS mean difference -14.6, P = .0140 and -10.9, P = .0746, respectively). The transition from octreotide to lanreotide was generally well-tolerated. CONCLUSION: Improvement in CS symptoms occurred with lanreotide treatment, regardless of prior octreotide use. ABBREVIATIONS: CI = confidence interval CS = carcinoid syndrome DB = double blind ELECT = Evaluation of Lanreotide depot/autogel Efficacy and safety as a Carcinoid-syndrome Treatment IOL = initial open-label IVRS/IWRS = interactive voice/web response system LS = least square NET = neuroendocrine tumor OR = odds ratio SC = subcutaneous SSA = somatostatin analogue SSTR = somatostatin receptor TEAE = treatment-emergent adverse event.

BIOCHEMICAL RESPONSES IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS WITH NEUROENDOCRINE TUMORS: POOLED ANALYSIS OF 2 PHASE 3 TRIALS.

OBJECTIVE: Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes. METHODS: Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly. RESULTS: Of 319 pooled patients, 86% and 95% had baseline 5-HIAA and CgA data, respectively, with 47% and 74% having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a decrease in biomarker levels at week 12, with statistical significance reached in the CgA cohort (not reached vs. 14.4 months; P<.0001). A large proportion (87%) of patients without symptoms of CS in the CLARINET study had detectable levels of 5-HIAA (48% >ULN). In ELECT, patients with CS who received lanreotide and experienced a biochemical response (≥50% decrease from baseline) achieved greater symptom control. CONCLUSION: This pooled analysis of two randomized, placebo-controlled trials demonstrated that 5-HIAA and CgA are secreted as biochemical biomarkers in many patients with NETs, regardless of clinical syndromes. Significant biochemical response was associated with improved clinical outcomes, as measured by improved PFS or improved CS symptom control. ABBREVIATIONS: 5-HIAA = 5-hydroxyindoleacetic acid; CgA = chromogranin A; CI = confidence interval; CLARINET = Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors; CS = carcinoid syndrome; ELECT = Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment; HR = hazard ratio; ITT = intention-to-treat; NET = neuroendocrine tumor; PanNET = pancreatic NET; PFS = progression-free survival; PPI = proton pump inhibitor; SSA = somatostatin analogue; ULN = upper limit of normal.

Cost of Treatment of Neuroischemic Ulcers of the Lower Extremity in Patients with Peripheral Artery Disease in the United States.

BACKGROUND: We evaluated the cost of treating neuroischemic ulcers of the lower extremity in patients with peripheral artery disease by using medical and hospital claims records submitted for reimbursement to payers (private insurance, Medicare, Medicaid). METHODS: Adjudicated claims and remittance data on claims that include submitted charges, line items paid by insurers directly to providers and patient payments of copays, deductibles and co-insurance were used. Eligible patients from a commercial database containing more than 60% of US patients with health insurance were analyzed. Patient selection, performed using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, yielded a study population of 42,837 unique anonymized patients. RESULTS: Using the metric of "submitted charges" to overcome differences in levels of reimbursement across insurance payers and Medicare/Medicaid, we identified 34,348 patients with ulcers with an average treatment cost of $94,100 per patient ($41,800 annualized) The costliest ulcer subtype was nonpressure ulcer of the heel/midfoot among 13,184 patients with $121,400 per patient ($53,900 annualized), 29% higher than across all ulcer types. The subset of 22,281 ulcer patients who also had a surgical procedure incurred costs of $121,000 per patient ($53,800 annualized). The costliest surgical codes were complications of vascular prosthetic devices, implants, grafts among 6444 patients with $146,900 per patient ($65,300 annualized). The combination of most expensive ulcer and most expensive surgery yielded a cohort of 2355 patients with the highest average cost of $177,400 per patient ($78,800 annualized). CONCLUSIONS: The resource burden for management of neuroischemic ulcers of the lower extremity in patients with peripheral artery disease is substantial. Mitigating this burden may help reduce significant resource utilization.