Emma Hitt, PhD

May 29, 2012

May 29, 2012 (Florence, Italy) — In patients with acromegaly, long-acting-release (LAR) pasireotide (SOM230, Novartis) was more effective than octreotide LAR (Sandostatin, Novartis) at inducing biochemical control and normalizing insulin-like growth factor 1 (IGF1) levels, according to the findings of a randomized trial.

Annamaria Colao, MD, PhD, from the Section of Endocrinology, Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples, Italy, and colleagues presented the findings here at an oral session at the Joint 15th International Congress of Endocrinology (ICE) and 14th European Congress of Endocrinology (ECE).

Currently available somatostatin analogues octreotide and lanreotide achieve disease control in a large proportion of patients, especially in the long term, Dr. Colao told Medscape Medical News. "However, only a minority are controlled after one year if treated first line."

She added that this study shows that pasireotide is demonstrated to be more efficacious than octreotide in patients treated first line, suggesting that "pasireotide might be a good first-line option."

According to Dr. Colao and colleagues, the broader somatostatin receptor–binding profile associated with pasireotide may improve response rates.

The current randomized, double-blind study compared pasireotide LAR with octreotide LAR during a 12-month period. The study included 358 patients with acromegaly, defined as growth hormone (GH) levels greater than 5 μg/L or GH nadir of 1 μg/L or less after an oral glucose tolerance test, and IGF1 level greater than the upper limit of normal.

Patients all were diagnosed for the first time with a visible adenoma on magnetic resonance imaging (MRI) or had undergone only pituitary surgery but had not received medication. They were randomly assigned to receive pasireotide LAR, 40 mg (n = 176), or octreotide LAR, 20 mg (n = 182), by once-monthly injection for 12 months.

After 3 and 7 months, the dose could be adjusted for either treatment (pasireotide LAR increased to 60 mg and octreotide LAR to 30 mg) for suboptimal biochemical response, although these increases were not required.

More than 80% of patients in each group completed 12 months of treatment, and dose was adjusted upward in 50.6% and 67.6% of pasireotide LAR and octreotide LAR recipients, respectively.

By 3 months, average GH and IGF1 levels decreased and remained suppressed. Of the patients, 31.3% in the pasireotide group achieved the primary endpoint (GH < 2.5 μg/L and normal IGF1 at 12 months) compared with only 19.2% of the octreotide group (P = .007). A total of 48.3% of pasireotide recipients and 51.6% of octreotide recipients had a mean GH level less than 2.5 μg/L (P = .536), respectively, whereas 38.6% and 23.6%, respectively, had normal IGF1 (P = .002).

In addition, patients receiving pasireotide were 63% more likely to achieve full biochemical control than were those receiving octreotide, whereas symptoms improved and tumor volume was reduced to a similar extent in both groups.

Most adverse effects were mild or moderate, and, except for hyperglycemia, pasireotide generally resulted in fewer adverse events. The most common adverse events with pasireotide vs octreotide, respectively, 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%).

"We still need a drug able to control 100% of patients and without side effects," Dr. Colao said, but if approved, pasireotide might be an option in patients whose disease is incompletely controlled with octreotide, she said.

Session moderator Martin Reincke, MD, professor of medicine at the Medizinische Klinik Innenstadt at the University of Munich, Germany, noted that the study contains new data demonstrating that pasireotide is more effective than the standard octreotide in inducing biochemical control of acromegaly.

"We have 3 goals in treating acromegaly," Dr. Reincke told Medscape Medical News. "One is to improve symptoms/quality of life; the second is to control tumor size; and the third is to reduce GH and IGF concentrations to safe levels."

According to Dr. Reincke, this study shows that with respect to the first 2 goals, pasireotide and octreotide appear to be similar, but with respect to the third goal of reducing GH and IGF concentrations, pasireotide is clearly more effective.

He added that the superior effects of pasireotide in controlling GH and IGF come at the expenses of a higher incidence of hyperglycemia. "Clinicians have to check blood glucose levels carefully," he said.

Pasireotide is an orphan drug currently in phase 3 studies for the treatment of Cushing disease, acromegaly, and gastroenteropancreatic neuroendocrine tumors. Pasireotide is a somatostatin analogue that has a 40-fold increased affinity to somatostatin receptor 5 compared with other somatostatin analogues and is being developed by Novartis.

The study was funded by Novartis. The authors have disclosed no relevant financial relationships. Dr. Reincke reports that he has received remuneration as an invited speaker by Novartis, Pharmacia, and Ipsen. He has participated in advisory boards of Novartis.

Joint 15th International Congress of Endocrinology (ICE) and 14th European Congress of Endocrinology (ECE). #OC1.1. Presented May 7, 2011.

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