Pasireotide in the Personalized Treatment of Acromegaly

Abstract

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

Clinical, hormonal and pathomorphological markers of somatotroph pituitary neuroendocrine tumors predicting the treatment outcome in acromegaly

“…Coopmans et al (24) showed that biochemical response to pasireotide-LAR is associated with high T2-signal intensity, whereas patients with a lower SST2 receptor expression have a greater chance to achieve tumor shrinkage. In general, good candidates for pasireotide treatment might be patients poorly responding to first-generation SRLs with high expression of SST5 receptor, with low AIP expression, those with SG tumors and with high Ki-67 index (49). The importance of clinical factors in terms of response to pasireotide-LAR has not been so widely discussed as molecular factors.…”

Pasireotide—a novel somatostatin receptor ligand after 20 years of use

“…sparsely granulated adenomas with low SSTR2 and E-cadherin expression, high SSTR5 expression, and low AIP and high Ki-67 expression, the recommended treatment of choice is PAS-LAR (Table 2 ). However, these recommendations should be verified in larger populations of patients with acromegaly [ 52 ]. Chiloiro et al evaluated the efficacy of PEGV and PAS-LAR in 74 patients resistant to first-generation SRLs therapy.…”

“…Radiological, molecular and pathologic factors influencing response to the different SRLs in the medical treatment of acromegaly[50][51][52] …”

Problems of diagnosis and treatment of acromegaly

“…При преимущественном воздействии на 5-й подтип соматостатиновых рецепторов он способен стабильно блокировать секреторную и пролиферативную активность опухолевых клеток, предотвращая дальнейшее развитие патологических изменений. Среди нежелательных явлений, возникающих при приеме продленной формы пасиреотида, следует отметить высокий риск нарушения углеводного обмена, что ограничивает его широкое применение [21].…”