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

Discussion

The treatment of patients affected by acromegaly can be extremely challenging, especially in cases of aggressive disease. The present series included a group of six patients with aggressive acromegaly, as suggested by the elevated GH expression, dimensions and invasiveness of the tumor, high proliferative index (Ki-67) expression, and failure to control the acromegaly with conventional SSAs (alone and combined with pegvisomant) and pasireotide. These patients consequently required combination therapy with pegvisomant and pasireotide for control of acromegaly. In one patient, shrinkage of the residual somatotropic pituitary adenoma occurred with this combination therapy.

The results from the present study have underlined the importance of personalized treatment in patients with acromegaly resistant to conventional SSAs and requiring second-line therapy. In the present series, the histopathological pattern of SSTRs was used to guide the therapeutic choice of switching from conventional SSAs to second-generation SSAs. It is well known that the main predictive factors of resistance to conventional SSAs are the lack of SSTR2 expression, a low SSTR2/SSTR5 ratio, younger patient age, male sex, high GH levels, high Ki-67 expression, high nuclear expression of theMCM7 labeling index, AIP mutation, and the sparsely granulated pattern of cytokeratin in the somatotropic pituitary adenoma.[1,8–10] Similarly, the expression of SSTR5 can predict the response to pasireotide.[5] In these series, combination therapy with pegvisomant allowed the IGF-I levels to normalize, according to the age-adjusted reference range. Moreover, four patients were also treated with a dopamine agonist. This treatment was prescribed to patients with a mammosomatotropic pituitary adenoma and secretion of both GH and prolactin. The main limitation of the present study was the small sample size of the study population, which limited the statistical significance of our data. However, our study was a pilot study, and the findings suggest the importance of a large, multicenter, and prospective trial. Moreover, to the best of our knowledge, our data, for the first time, have described a consecutive series of patients efficaciously treated with combination therapy of pasireotide and pegvisomant. Our results have shown that combined treatment with pasireotide and pegvisomant can induce control of aggressive acromegaly.

In conclusion, our findings have reinforced the importance of personalized treatment for patients with acromegaly, according to the clinical, biochemical, molecular, and morphological disease markers. Our findings also suggest the usefulness of a multidrug treatment approach with the combination of pegvisomant and pasireotide to achieve disease control in patients with acromegaly resistant to other therapeutic modalities.

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