Pasireotide Improves IGF-1 in Patients Resistant to Somatostatin Analogs

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Of the 4 participants whoes HbA1c rose over 9%, 2 required additional insulin added to their treatment regimen.
Of the 4 participants whoes HbA1c rose over 9%, 2 required additional insulin added to their treatment regimen.

Pasireotide may help insulin-like-growth-factor 1 (IGF-1) reach normal levels in patients with acromegaly who have previously been resistant to treatment with somatostatin analogs, according to a study published in Endocrine.

Study investigators sought to evaluate the efficacy and safety of pasireotide in patients with somatostatin-resistant acromegaly through a retrospective study. The study included 35 patients who were resistant or partially resistant to commercially available somatostatin analogs, such as octreotide, long-acting release pasireotide, or lanreotide autogel. All patients had been treated with somatostatin analogs as monotherapy for at least 6 months and had not achieved IGF-1 normalization.

Some patients in the cohort were also treated with pegvisomant previously to achieve hormonal remission. Treatment with pasireotide was initiated after discontinuation of somatostatin analogs and pegvisomant. Serum growth hormone (GH) and IGF-1 were measured after fasting, and hormonal control was defined as the patient achieving normal sex and age-adjusted IGF-1 levels throughout the treatment with pasireotide. Mean IGF-1 at diagnosis was 3.1 ± x 1.3 upper limit of normal range ([ULN] median; 2.93 x ULN) for age and gender. Long-acting release pasireotide was administered at a dose of 60 mg/4 weeks or 40 mg/4 weeks. Nineteen patients achieved normalization of IGF-1. IGF-1 was partially controlled in 5 patients, and 2 patients experienced significant improvement in disease control (IGF-1 suppression ≥50%, but still above 1.2 x ULN). Treatment with pasireotide had no effect in 9 patients. In all, 26 out of the 35 patients from the cohort benefited from pasireotide.

Several patients reported resolution of disease-related symptoms such as headaches after treatment. In most patients, IGF-1 normalization could be detected as early as after 1 or 2 pasireotide injections. Despite the beneficial effects on IGF-1 and symptomatology, a number of detrimental side effects were reported. Two patients developed symptomatic cholelithiasis, prompting 1 to discontinue treatment with pasireotide. Mean fasting glucose levels increased from 109 ± 28mg/dL at baseline to 138± 37mg/dL after treatment. Mean glycated hemoglobin increased accordingly. Seventeen patients required initiation or intensification of antidiabetic treatment.

The results of the study suggest that a considerable amount of patients with acromegaly who have shown resistance to first generation somatostatin analogs may benefit from treatment with monthly injections of pasireotide. Fifty percent of the patients in this cohort achieved normalization of IGF-1 levels. In addition, 83% of the patients that had a beneficial response to treatment improved with the lower dose of pasireotide. Despite the tradeoff in regard to high glucose control deterioration in 63% of patients, the majority (54%) of patients with acromegaly who have shown uncontrolled somatostatin resistance benefited from treatment with long-acting release pasireotide in regard to IGF-1 normalization.

These results are consistent with other pasireotide trials, although the higher response reported by this study may be due to a higher rate of pituitary surgery in this cohort. The study also had other limitations such as the lack of GH measurements as well as the absence of pituitary imaging during treatment.

Multiple authors declare affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors' disclosures.

Reference

Shimon I, Adnan Z, Gorshtein A, et al. Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study [published online July 26, 2018]. Endocrine. doi: 10.1007/s12020-018-1690-5

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