Emma Hitt, PhD

May 16, 2012

May 16, 2012 (Florence, Italy) — Pegvisomant appears to be effective and safe for patients with acromegaly resistant to other treatments, the ACROSTUDY shows.

Antonio Bianchi, MD, from the Catholic University in Rome, Italy, and colleagues presented the findings here at Joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology.

"The study confirms the efficacy of pegvisomant on acromegaly with resistance to other available medical treatments," Dr. Bianchi told Medscape Medical News. This "increases the reassurance that during pegvisomant, the rates of pituitary tumor enlargement, liver test elevations, and injections-site reactions are very low," the researchers report.

The study was designed to assess the effectiveness and safety of long-term pegvisomant in patients with acromegaly. The study was started in 2007; the current analysis involved 185 patients treated for an average duration of a little more than 3.0 years. The longest treatment course was 8.5 years.

Just under half of patients had undergone surgery, and nearly all patients had received a somatostatin analog with or without a dopamine agonist. Of 185 patients, 24 had received no previous treatment for acromegaly.

At the beginning of the study, 43.2% of patients received pegvisomant alone, 49.9% received pegvisomant plus a somatostatin analog, and 10% received the combination plus a dopamine agonist.

About three quarters of patients had documented normalization of insulin-like growth factor 1 levels after 1 and 5 years of treatment. With pegvisomant, tumor lesion size increased in 11 patients and decreased in 16 patients.

No sustained elevations in transaminases were noted. Two patients discontinued treatment because of serious adverse events

The data confirm that "long-term pegvisomant therapy is highly effective in acromegalic patients resistant to other treatment, and shows an excellent safety profile," Dr. Bianchi and colleagues conclude.

"There were very few adverse events with pegvisomant, and the biochemical control of acromegaly was achieved with a dose of pegvisomant that was not the highest recommended," Dr. Bianchi explained.

"In my opinion, we have 2 problems," he said. "In spite of the efficacy in patients with somatostatin-resistant disease, we have a few patients with more aggressive disease who are also resistant to pegvisomant," Dr. Bianchi said. He explained that the second issue is that 5 to 7 years is an adequate observation period, but in the future, "data on more patients for a longer period are necessary."

Independent commentator Andrea Guistina, MD, from the Department of Medical and Surgical Sciences at the University of Brescia in Italy, noted that these findings provide "further evidence in a large cohort of acromegalic patients, followed up for a long period of time, that pegvisomant in real-life clinical practice is almost as effective as it is in clinical trials in obtaining biochemical control of the disease"

"Clinically, the significance of this study is...related to the positive balance between the efficacy and safety of pegvisomant, which is reassuring for the clinical endocrinologist," Dr. Guistina told Medscape Medical News.

According to Dr. Guistina, the findings suggest that a variance between clinical trials and actual practice has emerged in a small subpopulation of acromegalic patients resistant also to pegvisomant.

"An interesting new challenge will be to identify the mechanism underlying this resistance," she said.

The ACROSTUDY Italy is sponsored by Pfizer. Dr. Guistina reports being a consultant for Ipsen, Italfarmaco, Novartis, and Pfizer.

Joint 15th International Congress of Endocrinology (ICE) and 14th European Congress of Endocrinology (ECE): Abstract OC1.3. Presented May 7, 2012.