Pasireotide versus octreotide in acromegaly: a head-to-head superiority study

Abstract

Context: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control.

Objective: Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly.

Design and setting: We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries.

Patients: A total of 358 patients with medically naive acromegaly (GH >5 μg/L or GH nadir ≥1 μg/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging.

Interventions: Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60 mg or octreotide LAR 30 mg was permitted, but not mandatory, if GH ≥2.5μg/L and/or IGF-1 was above the upper limit of normal.

Main outcome measure: The main outcome measure was the proportion of patients in each treatment arm with biochemical control (GH <2.5 μg/L and normal IGF-1) at month 12.

Results: Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% vs 19.2%; P = .007; 35.8% vs 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P = .002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH <2.5 μg/L. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% vs 21.7%).

Conclusions: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.

Figure 1.

Proportion of patients in the overall population, postsurgery stratum and de novo stratum with GH <2.5 μg/L and normal IGF-1 after 12 months of treatment with pasireotide LAR or octreotide LAR. *, P = .007 pasireotide LAR vs octreotide LAR in the overall population. The study was not powered to detect treatment differences in subgroups. The 95% CI of the OR in favor of pasireotide LAR reached statistical significance at the .05 level for postsurgery patients (OR, 2.34 [95% CI, 1.14–4.79]) but not de novo patients (OR, 1.65 [95% CI, 0.85–3.23]).

Figure 2.

Mean ± SE GH levels (A) and standardized IGF-1 levels (B) over time by treatment group. The numbers at the bottom of each graph are the numbers of patients in the pasireotide LAR/octreotide LAR treatment groups. Standardized IGF-1 is the IGF-1 value divided by the ULN range.

Figure 3.

Percent change in tumor volume from baseline to month 12 in patients with baseline and month-12 MRI assessments.