Pasireotide LAR is significantly more effective than octreotide LAR at inducing biochemical control in patients with acromegaly: results of a 12-month randomized, double-blind, multicenter, Phase III study
A. Colao1, M. Bronstein2, P. Freda3, F. Gu4, C. Shen5, M. Gadelha6, M. Fleseriu7, K. Hermosillo Reséndiz8, M. Ruffin9, Y. Chen8 & M. Sheppard10
Author affiliations
1University of Naples ‘Federico II’, Naples, Italy; 2University of São Paulo Medical School, São Paulo, Brazil; 3Columbia University, College of Physicians and Surgeons, New York, New York; 4Ministry of Health, Peking Union Medical College Hospital, Beijing, China; 5National Yang-Ming University, Taipei, Taiwan; 6Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 7Oregon Health and Science University, Portland, Oregon, USA; 8Novartis Pharmaceuticals Corporation, Florham Park, New Jersey, USA; 9Novartis Pharma AG, Basel, Switzerland; 10University of Birmingham, Edgbaston, Birmingham, UK.
Introduction: Using the criterion of GH<2.5 μg/l and normalized IGF1, response rates to currently available somatostatin analogues in medically-naïve patients with acromegaly are 20–25% after 12 m. The broader somatostatin receptor binding profile of pasireotide may potentially improve response rates. This randomized, double-blind 12-m study compared pasireotide LAR with octreotide LAR.
Methods: Patients with acromegaly (GH>5 μg/l or GH nadir ≥1 μg/l post-OGTT, and IGF1>ULN) who were de novo with a visible adenoma on MRI or medically-naïve (no previous medical therapy but prior pituitary surgery) received pasireotide LAR 40 mg/28d (n=176) or octreotide LAR 20 mg/28 d (n=182) for 12 m. At 3 and 7 m, dose titration to pasireotide LAR 60 mg or octreotide LAR 30 mg for suboptimal biochemical response was permitted, but not mandatory. Primary objective: comparison of the proportion of patients in each arm with GH<2.5 μg/l and normal IGF1 at 12 m. GH was measured as a 5-point mean (2 h curve).
Results: At baseline, mean GH was 21.9 and 18.8 μg/l in the pasireotide LAR and octreotide LAR arms, respectively; mean IGF1 was 2.6×ULN and 2.8×ULN. 80.1 and 85.7% of pasireotide LAR and octreotide LAR recipients completed 12 m. Dose uptitration was performed in 50.6 and 67.6% of pasireotide LAR and octreotide LAR recipients. Mean GH and IGF1 decreased by 3 m and remained suppressed. The primary endpoint was achieved by 31.3 and 19.2% of pasireotide LAR and octreotide LAR recipients (P=0.007); 48.3 and 51.6% had mean GH<2.5 μg/l (P=0.536); 38.6 and 23.6% had normal IGF1 (P=0.002). Pasireotide LAR recipients were 63% more likely to achieve full biochemical control than octreotide LAR recipients. Symptom improvement and tumor volume reduction were similar in both groups. The most common AEs with pasireotide LAR vs octreotide LAR were diarrhea (39.3 vs 45.0%), cholelithiasis (25.8 vs 35.6%), headache (18.5 vs 26.1%) and hyperglycemia (28.7 vs 8.3%). Most AEs were mild or moderate.
Conclusions: In the largest randomized study of a medical therapy in patients with acromegaly, pasireotide LAR was significantly more effective at inducing full biochemical control, as well as normal IGF1, than the current standard medical therapy octreotide LAR, with an acceptable safety profile.
Declaration of interest: The authors declare that there is a conflict of interest.
Funding: This work was supported, however funding details are unavailable.