The medical treatment with pasireotide in Cushing’s disease: an Italian multicentre experience based on “real-world evidence”

Abstract

A phase III study has demonstrated that 6-month pasireotide treatment induced disease control with good safety in 15–26% of patients with Cushing’s disease (CD). The aim of the current study was to evaluate the 6-month efficacy and safety of pasireotide treatment according to the real-world evidence. Thirty-two CD patients started pasireotide at the dose of 600 µg twice a day (bid) and with the chance of up-titration to 900 µg bid, or down-titration to 450 or 300 µg bid, on the basis of urinary cortisol (UC) levels or safety. Hormonal, clinical and metabolic parameters were measured at baseline and at 3-month and 6-month follow-up, whereas tumour size was evaluated at baseline and at 6-month follow-up. At baseline, 31 patients had very mild to moderate disease and 1 patient had very severe disease. Five (15.6%) patients discontinued treatment for adverse events; the remaining 27 patients (26 with very mild to moderate disease and 1 with very severe disease), reached 6-month follow-up. Considering the group of patients with very mild to moderate disease, responsiveness, defined by the normalization (<1 the upper limit of normal range, ULN) or near normalization (>1 and ≤1.1 ULN) of UC levels, was registered in 21 patients (full control in 19 and near control in 2), corresponding to 67.7% and 80.8% according to an “intention-to-treat” or “per-protocol” methodological approach, respectively. Weight, body mass index, waist circumference, as well as total and LDL-cholesterol significantly decreased, whereas fasting plasma glucose and glycated haemoglobin significantly increased. Hyperglycaemia was documented in 81.2%, whereas gastrointestinal disturbances in 40.6% of patients. In conclusion, in the real-life clinical practice, pasireotide treatment normalizes or nearly normalizes UC in at least 68% of patients with very mild to moderate disease, with consequent improvement in weight, visceral adiposity and lipid profile, despite the occurrence or deterioration of diabetes in the majority of cases, confirming the usefulness of this treatment in patients with milder disease and without uncontrolled diabetes.

Biological and Biochemical Basis of the Differential Efficacy of First and Second Generation Somatostatin Receptor Ligands in Neuroendocrine Neoplasms

“…Lastly, a very recent study by Pivonello & Coll. evaluated the efficacy and safety of PAS treatment, according to the real-world evidence [144]. This study, performed on 23 CD patients, demonstrated that, in the real-life clinical practice, a six-month treatment with PAS normalizes, or nearly normalizes, UFC in about 68% of patients with a very mild to moderate disease.…”

Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, Expanded-Access Study

“…In the studies carried out in this setting to date, the results have supported the findings from prospective studies. In one study conducted in five Italian centers, 68% of patients with mild–moderate disease ( N = 31) achieved a response to pasireotide (defined as normalization or near normalization of UFC [<1.0–1.1 × ULN]) after 6 months of treatment, which was accompanied by improvements in clinical signs and symptoms (19). The safety profile of pasireotide was consistent with that previously observed during the Phase III study of pasireotide in Cushing's disease (16), with hyperglycemia a frequent (81% of patients) but manageable side effect (study goal of HbA 1c <7.5% achieved in 65% of patients).…”

Glucocorticoid excess and COVID-19 disease

“…In CD patients, the pituitary-directed agents pasireotide and cabergoline may also be evaluated as treatment options for hypercortisolism control during a COVID-19 pandemic, although their intermediate efficacy, with hormonal control reached in 25% and 31% of treated patients, respectively [ 67 ], should limit their use as second-line approaches except for patients with mild CS [ 28 , 83 ]. In particular, pasireotide should not be preferred, due to hyperglycaemia-related adverse events, which may occur in up to 73% of treated patients [ 67 , 84 – 86 ], and to the higher morbidity and mortality in COVID-19 patients with diabetes mellitus [ 2 ].…”