Introduction: Pasireotide long acting release (LAR) is approved for second line treatment of acromegaly. We present 3 patients with aggressive acromegaly treated with a personalized de-escalation approach.
Case 1: A 61-year-old female affected by acromegaly reisistant on first-line SSAs. In 2015 therapy was switched to pasireotide LAR 60 mg every 28 days. After two years, the IGF-I level touched the lower age range and therapy was downscaled to pasireotide LAR 40 mg, and in 2020 to 20 mg. In 2021 and 2022, the IGF-I level remained within the normal age range.
Case 2: A 40-year-old female affected by acromegaly resistant on first line SSAs and pegvisomant, who underwent on 3 different neurosurgeries. In 2011 he was enrolled in a Phase III clinical trial (PAOLA study) and assigned to receive pasireotide LAR (60 mg every 28 days). Due to IGF-I overcontrol and radiological stability, in 2016 therapy was downscaled to pasireotide LAR 40 mg and in 2019 further downscaled to pasireotide LAR 20 mg. During the treatment, the patient developed hyperglycemia treated with metformin 500 mg 3 times daily.
Case 3: A 37-year-old male affected by acromegaly resistant on first line SSAs. In 2011 the patient was enrolled in the PAOLA study assigned to receive pasireotide LAR (60 mg every 28 days). In 2018, therapy was downscaled to pasireotide LAR 40 mg for IGF-I overcontrol and in 2022 to pasireotide 20 mg. He developed hyperglycemia, HbA1c values stayed under 6.5% (48 nmol/l) for 7 years.
Discussion: Initiating therapy with a high dose of pasireotide (60 mg) could allow a greater proportion of patients to achieve acromegaly control, particularly in selected cases of clinically aggressive acromegaly that may respond well to pasireotide (characterized by high IGF-I values at diagnosis, invasion of the cavernous sinuses, partial resistance to first-line SSAs and positive expression of SSTR5). Another benefit of this treatment could be the long-term control of IGF-I levels and its oversuppression that continues even when the dose of pasireotide LAR is reduced. The major risk seems to be hyperglicemia. Nevertheless, GH and IGF-I uncontrolled levels are major players in the glucose metabolism. The main limitation of our observation is the very small sample size of our series, to confirm our observations clinical studies are required.
Conclusion: This de-escalation pasireotide treatment could allow to both achieving control of acromegaly and acceptable metabolic tolerance in selected cases of aggressive acromegaly potentially responsive to pasireotide.
13 May 2023 - 16 May 2023