Pasireotide and Pegvisomant Combination Treatment in Acromegaly Resistant to Second Line Therapies: A Longitudinal Study

INTRODUCTION: The treatment of acromegaly resistant to first and second line therapies may be extremely challenging. AIM, PATIENTS AND METHODS: To describe our patients successfully treated with a combination therapy of Pasireotide LAR and Pegvisomant and to compare with a control group of patients resistant to conventional somatostatin analogues (SSAs) and controlled with other treatments, such as Pasireotide LAR (in monotherapy) and Pegvisomant (in monotherapy or in association with conventional SSAs). RESULTS: A total of 6 patients reached acromegaly disease control with Pasireotide Lar and Pegvisomant combination treatment, after failure with all other treatments. As compared to the 49 patients of the control group, these 6 patients carried giant and invasive pituitary adenomas (both at the cavernous sinus and at other structures). Although not statistically significant, higher values of growth hormone at acromegaly diagnosis, a more elevated Ki67, a higher expression of the subtype 5 and a lower expression of the subtype 2 of the somatostatin receptor were detected in patients on a combination treatment with Pasireotide Lar and Pegvisomant, as compared to the control group. CONCLUSION: Our data reinforced the importance of a personalized treatment of acromegaly, according to clinical, biochemical, molecular and morphological disease markers and suggests that the associative treatment with Pasireotide LAR and Pegvisomant can induce disease control in tumors with a low expression of SSTR2, resistant to conventional SSAs (alone or in association with Pegvisomant) and to new generation SSAs alone (Pasireotide LAR).