Acromegaly is a morbid condition mainly caused by overproduction of growth-hormone (GH) from a pituitary adenoma leading to excessive growth. Normalisation of insulin-like growth factor-1 (IGF1) is an important goal for the treatment of acromegaly. The second-generation somatostatin analog (SSA) long acting pasireotide (la-PAS) has recently been introduced for the management of patients uncontrolled by first-generation SSA. The ACRONIS study (CSOM230CIC05) will provide real-world evidence on the efficacy and safety of la-PAS in acromegaly patients from twelve countries, either already treated with monthly la-PAS for ≥6 months (retrospective set) or going to be treated (prospective set). Results of the first interim analysis reflecting the retrospective set are presented. The mean age of the enrolled retrospective patients (n=60) was 45.4 years; 55% female and 76.7% Caucasian. Mean time since diagnosis was 53.2 months (S.D. 54.5 months); 83.3% had previous surgery and 40.0% radiotherapy. 98.3% had taken prior medication: mainly first-generation SSAs (73.3% octreotide, 31.7% lanreotide), growth hormone receptor antagonists (53.3%) or dopamine agonists (48.3%) in mono- or combination therapy, respectively. 23.3% and 13.3% of patients were diabetic or pre-diabetic prior to la-PAS prescription, respectively. All patients were la-PAS naïve at baseline. 81.4% of patients started with la-PAS 40mg, 1.7% with 20mg and 16.9% with 60mg. After a mean duration of 8.2 months (range 625 months, n=59 (all patients within the retrospective set having ≥1 post-baseline safety assessment and with ≥1 dose of la-PAS)), 62.7% remained on starting dose, 32.2% were up-titrated, 5.1% down-titrated. At 6 months, IGF1 was normalised [≤1 times upper limit of normal (ULN)] in 42.5%, (n=40). IGF1 normalisation and GH <1 (<2.5 μg/l) was achieved by 14.3% (21.4%) of 28 evaluable patients. These results are in line with the pivotal PAOLA study (NCT01137682) where 25% and 26% of patients on the 40 mg (n=65) and 60 mg (n=65) doses, respectively, achieved normalised IGF values; 15.4% and 20% respectively, achieved both IGF1 <1 ULN and GH <2.5 μg/l. The adverse events (AEs) most commonly reported were diabetes mellitus (18.6%), hyperglycaemia (13.6%), headache (10.2%) and diarrhoea (10.2%). The only reported grade 3/4 AE was headache (1.7%). The overall percentage of glucose metabolism-related AEs (33.9%) seems lower than previously reported. The safety profile of la-PAS in the ACRONIS study was consistent with its known safety profile. In conclusion, the results of retrospective ACRONIS dataset confirm the efficacy and tolerability of long-acting pasireotide in previously uncontrolled acromegaly patients in clinical practice.
19 May 2018 - 22 May 2018