Signifor Reduces Pituitary Tumor Size in Cushing’s Patients: Study

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by Steve Bryson, PhD |

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Signifor (pasireotide), a treatment for Cushing’s disease patients for whom surgery failed or is not an option, significantly reduces the size of benign pituitary tumors in more than 40% of people with the condition, according to a review of published studies.

However, the researchers noted that tumor reduction was not a main goal in any of the studies and that most patients had undergone surgery before receiving Signifor, which may limit the findings.

“Further studies, with longer treatment observation, may reveal whether [Signifor] may achieve significant tumor shrinkage in these patients,” the researchers wrote.

The review study, “Pasireotide-Induced Shrinkage in GH and ACTH Secreting Pituitary Adenoma: A Systematic Review and Meta-Analysis,” was published in the journal Frontiers in Endocrinology.

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Signifor Controlled Patient’s Cortisol Fluctuations

Cushing’s disease is mostly caused by benign, or noncancerous, tumors in the pituitary gland, which stimulate the excessive production of adrenocorticotropic hormone (ACTH). This hormone causes the adrenal glands, which sit atop the kidneys, to release too much cortisol, leading to symptoms.

Usually, the first treatment option for Cushing’s disease patients is to surgically remove the benign pituitary tumor, also known as a corticotroph adenoma. Alternatively, patients may receive Signifor.

Signifor, marketed by Recordati, was the first medication approved for adults with Cushing’s disease who were ineligible for surgery or whose tumor came back after surgery.

A lab-made version of the naturally occurring hormone somatostatin, it activates the somatostatin receptor in the pituitary tumor and decreases ACTH production, which eventually leads to cortisol reductions.

Signifor’s approval in 2012 was based on data from the Phase 3 B2305 trial (NCT00434148). The trial enrolled 162 patients and randomly assigned them to receive 600 or 900 micrograms (mcg) of Signifor via subcutaneous (under-the-skin) injections twice daily.

The medication brought cortisol levels back to normal in up to 26% of patients and improved several symptoms of the disease. Signifor reduced tumor volume in many participants, a later analysis also suggested.

Signifor could also shrink pituitary tumors in people with acromegaly, a hormonal disorder that develops when the pituitary gland produces too much growth hormone during adulthood. This condition is caused by a different type of benign pituitary tumor called somatotroph adenoma.

Signifor’s effects on Cushing’s, acromegaly

To confirm the effect of Signifor on tumor size in people with Cushing’s disease and acromegaly, researchers at the University of Padova, Italy conducted a systematic review and meta-analysis of published studies.

A meta-analysis is a statistical method that combines data from multiple scientific studies to calculate an overall effect. Because they includes data from a much larger population, meta-analyses are usually more precise than individual studies at determining a certain approach’s impact.

The researchers looked for studies involving people with Cushing’s disease or acromegaly who had information on tumor size during treatment with Signifor. The database search yielded three studies that fulfilled the criteria for Cushing’s and six for acromegaly.

The Cushing’s studies included 139 patients, most of whom were treated with Signifor as a second-line treatment after failing to respond to surgery.

Only 34 patients had an available pituitary MRI to determine tumor size over time. Of them, 20 received Signifor by under-the-skin injection twice a day and 14 were given the long-acting formulation, Signifor LAR, which is injected into the muscle once a month.

Over a follow-up period that ranged from six months to five years, 41.2% of patients saw a significant reduction in tumor size during Signifor treatment.

The findings were similar for people with acromegaly. From a total of 265 patients with available tumor size data, 37.7% showed a significant tumor shrinkage following up to 25 months of treatment.

No evidence of publication bias for either condition was found. This occurs when the outcome of a study influences the decision to publish. Publishing only data showing significant findings skews the findings in favor of positive results.

“Our results strengthen the role of [Signifor] treatment in somatotroph and corticotroph adenomas, especially when tumor volume is a relevant issue,” the researchers said.

They noted that most Cushing’s patients had micro-adenomas, or very small tumors, “suggesting that tumor size might be a less relevant issue during medical treatment, even if the “cure” of the disease may forecast the resolution of the adenoma.”

“Future research aiming to characterize markers predictive of response could help to identify optimal candidates for this treatment,” the researchers said.