Pasireotide and Pegvisomant Combination Treatment in Acromegaly Resistant to Second-Line Therapies

A Longitudinal Study

Sabrina Chiloiro; Chiara Bima; Tommaso Tartaglione; Antonella Giampietro; Marco Gessi; Liverana Lauretti; Carmelo Anile; Cesare Colosimo; Guido Rindi; Alfredo Pontecorvi; Laura De Marinis; Antonio Bianchi

Disclosures

J Clin Endocrinol Metab. 2019;104(11):5478-5482. 

In This Article

Abstract and Introduction

Abstract

Context: The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging.

Design: We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs).

Results: In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group.

Conclusion: Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).

Introduction

Medical treatment of acromegaly is based on first-line [e.g., conventional somatostatin analogs (SSAs)] and second-line (e.g., pegvisomant and pasireotide) therapies.[1–5] The outcomes of first-generation SSAs and of pegvisomant and pasireotide have been largely described, as have those of a combination treatment with conventional SSAs and pegvisomant.[2]

Interest in combination therapies has been increasing in recent years, because the synergistic effect of the drugs can improve the treatment outcomes. However, only one case of combination treatment with pasireotide and pegvisomant has been reported.[6]

We have described our case series of patients who were successfully treated with combination therapy consisting of pasireotide and pegvisomant and compared their clinical features with those of a control group.

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