ACROSTUDY: Pegvisomant safe, effective for long-term use in acromegaly
Real-world data from the long-term ACROSTUDY show the growth hormone receptor agonist pegvisomant is safe and effective, with a low incidence of liver enzyme elevation and no increase in tumor size for most patients with acromegaly.
In a comprehensive review of the ACROSTUDY, initiated in 2004 to investigate the long-term effects of pegvisomant (Somavert, Pfizer) in a real-world, international cohort, researchers confirmed the overall favorable risk-benefit profile and high efficacy of pegvisomant as monotherapy and combination therapy in patients with aggressive, uncontrolled or active acromegaly requiring long-term medical therapy.
“The global, multicenter, noninterventional ACROSTUDY looked at outcomes for pegvisomant in monotherapy and combination therapy, with the main focus on safety,” Endocrine Today Editorial Board Member Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health & Science University in Portland, told Healio. “Pegvisomant had a favorable safety profile in clinical practice, especially concerning pituitary tumor volumes and liver tests. We found a low incidence of liver enzyme elevation during pegvisomant treatment, not different from previous reports. The percentage of patients with [insulin-like growth factor I] levels within the normal range increased from 53.7% at year 1 to 63.3% at year 5, and remained above 60% (63.3%-79.3%) throughout most of the study. Importantly, pegvisomant doses in patients with active acromegaly also increased over time and were higher than those in controlled patients at most years.”
Fleseriu and colleagues analyzed data from 2,221 adults with acromegaly treated with pegvisomant before the ACROSTUDY or at enrollment (median treatment duration, 9.3 years) and followed for a median of 7.4 years. Primary endpoints were long-term safety and efficacy, as defined by changes in IGF-I.
Before initiating pegvisomant, 96.3% of participants received other surgery, radiotherapy or medications to treat acromegaly; 87.2% reported comorbidities.
During the ACROSTUDY, researchers observed 5,567 adverse events in 56.5% of participants, with 613 considered treatment-related in 16.5% of participants (leading to drug withdrawal in 1.3%).
Pituitary imaging showed a tumor size increase in 7.1% of participants; however, 71.1% reported no changes. Abnormal aspartate aminotransferase or alanine aminotransferase liver tests occurred in 3.2% of patients. IGF-I normalization rate improved over time, increasing from 11.4% when initiating pegvisomant to 53.7% at year 1, and reaching 75.4% at year 10 with use of at least 30 mg pegvisomant per day in an increasing proportion of patients.
Fleseriu noted that lipodystrophy may be associated with loss of biochemical control for patients with previous control; therefore, the injection site should be monitored for lipodystrophy and frequent injection-site changes.
“This outcome was very rare and occurred in less than 2% of participants,” Fleseriu said.
Fleseriu said increased awareness about acromegaly and early diagnosis — which is still delayed for up to 11 years — is needed.
“Earlier on in the course of the disease, many patients have smaller pituitary adenomas, and thus, surgery would have a higher likelihood of cure,” Fleseriu said. “There have been several developments in medical therapies. Oral somatostatin receptor ligands are now available and seem to improve symptom control in some patients. No combination therapy is approved, but its use, especially for somatostatin receptor ligands plus pegvisomant, has significantly increased with better control. Recent data show even weekly or biweekly pegvisomant would be efficacious and cost-effective in combination with low-dose somatostatin receptor ligands.”