Endocrine Abstracts

Introduction: A robust clinical programme of 14 trials demonstrated pasireotide as an effective treatment for patients with rare endocrine disorders, including acromegaly and Cushing’s disease (CD). Patients with acromegaly or CD have significant morbidity, reduced quality of life and, if inadequately treated, higher mortality risk than the general population. This 8-year interim analysis evaluated long-term safety of pasireotide treatment in patients with acromegaly, CD or other endocrine disorders.

Methods: This ongoing, open-label, multicentre study allows continued treatment for patients who completed a previous pasireotide parent trial (NCT01794793). Patients who continued receiving clinical benefit, according to the parent study investigator, entered the rollover study and remained on pasireotide. Depending on the administration route in the parent study, patients received pasireotide long-acting release (LAR; n=303) or subcutaneous (sc; n=38) as monotherapy (n=36), or sc combined with cabergoline (n=2). The primary objective was to evaluate long-term safety, determined by frequency of adverse events (AEs)/serious adverse events (SAEs).

Results: Overall, 341 patients from 29 countries have entered the study from 14 parent studies: 228 patients had acromegaly, 64 had CD and 49 had other endocrine disorders, including melanoma, dumping syndrome and neuroendocrine tumours. Median (min−max) exposure to all pasireotide formulations from rollover baseline to data cut-off and across all indications was 45.3 months (0.9–100.8). Median (min−max) dose from rollover baseline was 45.4 mg/month (5.3–128.3) with pasireotide LAR and 1200 µg/day (300–1800) with pasireotide sc. Altogether, 89 (26.1%) patients discontinued treatment, most commonly because of consent withdrawal (n=21, 6.2%). The most common AEs during rollover (≥10% in all patients) were nasopharyngitis (acromegaly n=13, 5.7%; CD n=14, 21.9%; other diseases n=14, 28.6%), hyperglycaemia (acromegaly n=29, 12.7%; CD n=2, 3.1%; other diseases n=7, 14.3%), back pain (acromegaly n=20, 8.8%; CD n=7, 10.9%; other diseases n=8, 16.3%) and headache (acromegaly n=21, 9.2%; CD n=6, 9.4%; other diseases n=7, 14.3%). SAEs were reported in 87 (25.5%) patients, most commonly cholelithiasis and COVID-19 (both n=9, 2.6%). Overall, 18 (5.3%) patients discontinued treatment because of AEs. Incidence of new hyperglycaemia-related AEs during rollover was low. No new safety signals were identified.

Conclusions: Hyperglycaemia is an expected AE during pasireotide treatment, often occurring in the first 3 months of therapy. These data support pasireotide as a well-tolerated long-term treatment in patients with acromegaly, CD or other endocrine disorders and affirm that patients receive long-term benefit, with a low discontinuation rate over 8 years.