Biochemical control is maintained with pasireotide LAR in patients with acromegaly: Results from the extension of a randomized phase III study (PAOLA)

Introduction: In a 24-week core phase of a randomized, Phase III study (PAOLA) which enrolled 198 patients with inadequately controlled acromegaly, significantly greater proportion of patients achieved biochemical control (defined as growth hormone [GH] level <2.5 μg/L andnormalized insulin-like growth factor [IGF]-1) with pasireotide long-acting release (LAR) 40 mg and 60 mg than with continued treatment with octreotide LAR 30 mg/lanreotide Autogel 120 mg (15.4% and 20.0% vs. 0%). Results from a preliminary analysis (data cut-off 3 June 2013) from the 28-week extension phase of this study are reported here. Methods: After completion of the core phase, patients continued receiving the same treatment during a 4-week bridging phase. Patients in pasireotide LAR (40 mg/60 mg) arms who had biochemical control at week 24 of the core study continued receiving double-blind pasireotide LAR at the same dose; those who were uncontrolled were started on open-label pasireotide LAR 60 mg. Patients in the active control arm (octreotide LAR/lanreotide Autogel) who were uncontrolled at week 24 of the core study were switched to open-label pasireotide LAR 40 mg (crossover arm). Key efficacy endpoints included (a) proportion of patients with biochemical control at extension week 28 (b) proportion of patients with GH< 2.5 μg/L or normal IGF-1 alone at extension week 28. Additionally, safety and tolerability were evaluated. Results: Of the 181 patients completing the core phase, 173 entered the extension (pasireotide LAR 40 mg, n=57; pasireotide LAR 60 mg, n=54; crossover, n=62). Among the patients with available data at extension week 28, the proportion of patients with (a) biochemical control was 18.4% (9/49), 33.3% (15/45), and 20.0% (10/50) (b) GH< 2.5 μg/L was 38.8% (19/49) 46.7% (21/45), and 42.0% (21/50); normal IGF-1 was 32.7% (16/49), 37.8% (17/45), and 24.0% (12/50), in the pasireotide LAR 40 mg, pasireotide LAR 60 mg, and crossover arms, respectively. Pasireotide LAR maintained biochemical control during the 28-week extension. Safety was consistent with the findings in the core phase; the most frequently reported adverse events were hyperglycemia, diabetes mellitus, cholelithiasis, and diarrhea. Conclusions: During the 28-week extension of PAOLA study, pasireotide LAR maintained biochemical control and was generally well tolerated in patients with acromegaly who were previously inadequately controlled by first-generation somatostatin analogues. These preliminary data seem to be consistent with data from the core study: around 20% of patients in the active control group achieved biochemical control after switching to pasireotide in the extension. Pasireotide LAR is a potential, viable, long-term treatment option for patients with acromegaly.