Endocrine Abstracts (2014) 35 P907 | DOI: 10.1530/endoabs.35.P907

Pasireotide LAR demonstrates superior efficacy versus octreotide LAR and lanreotide ATG in patients with inadequately controlled acromegaly: results from a phase III, multicentre, randomized study (PAOLA)

Mônica Gadelha1, Marcello Bronstein2, Thierry Brue3,4, Mihail Coculescu5, Maria Fleseriu6, Mirtha Guitelman7, Vyacheslav Pronin8, Gerald Raverot9, Ilan Shimon10,11, Kayo Kodama Lievre12, Juergen Fleck12, Mounir Aout12, Alberto Pedroncelli12 & Annamaria Colao13

1Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2University of São Paulo Medical School, São Paulo, Brazil; 3Aix-Marseille University Centre National de la Recherche Scientifique, Marseille, France; 4Assistance Publique-Hôpitaux de Marseille, Marseille, France; 5National Institute of Endocrinology ‘CI Parhon’, Bucharest, Romania; 6Oregon Health & Science University, Portland, Oregon, USA; 7Hospital Carlos G Durand, Buenos Aires, Argentina; 8IM Sechenov First Moscow State Medical University, Moscow, Russia; 9Hospices Civils de Lyon, Lyon, France; 10Rabin Medical Center, Petah-Tiqva, Israel; 11Tel-Aviv University, Petah-Tiqva, Israel; 12Novartis Pharma AG, Basel, Switzerland; 13Università Federico II di Napoli, Naples, Italy.

Background: Some patients with acromegaly do not achieve biochemical control despite receiving maximum-approved doses of currently available somatostatin analogues. This 24-week, randomized study assessed the multireceptor-targeted somatostatin analogue pasireotide LAR vs octreotide LAR/lanreotide Autogel in patients with inadequately controlled acromegaly.

Methods: Eligible patients: ≥18 years with mean GH levels ≥2.5 μg/l and IGF1 levels >1.3×ULN (inadequate control) who had received octreotide LAR 30 mg or lanreotide Autogel 120 mg monotherapy for ≥6 months. Patients were randomized to: double-blind pasireotide LAR 40 or 60 mg; or continued treatment with open-label octreotide LAR/lanreotide Autogel (active control group). Primary endpoint: proportion of patients with biochemical control (GH <2.5 μg/l and normalized IGF1) at 24 weeks. Key secondary endpoint: proportion of patients with normalized IGF1; other secondary endpoints: proportion of patients with GH <2.5 μg/l; tumour volume reduction >25%; safety/tolerability.

Results: 198 patients were randomized: pasireotide LAR 40 mg (n=65), 60 mg (n=65), active control (n=68). Significantly more patients achieved biochemical control (15.4% and 20.0 vs 0%; P=0.0006 and P<0.0001 respectively) and IGF1 normalization (24.6% and 26.2 vs 0%; P<0.001 for both) with pasireotide LAR 40 and 60 mg vs active control at 24 weeks. Furthermore, more patients had GH levels <2.5 μg/l (35.4% and 43.1 vs 13.2%) and tumour volume reduction >25% (18.5% and 10.8 vs 1.5%) with pasireotide LAR 40 and 60 mg compared with active control. The safety profile of pasireotide LAR 40 and 60 mg was similar to that for the active control group, except for the frequency and degree of hyperglycaemia. The most common adverse events were hyperglycaemia (33.3, 30.6 and 13.6%), diabetes mellitus (20.6, 25.8 and 7.6%) and diarrhoea (15.9, 19.4 and 4.5%).

Conclusions: Pasireotide LAR provides superior efficacy over continued treatment with octreotide LAR/lanreotide Autogel in patients with long-standing, inadequately controlled acromegaly. Pasireotide LAR could become the new standard pituitary-directed treatment in patients with acromegaly inadequately controlled by sst2-preferential somatostatin analogues.