How to Position Pasireotide LAR Treatment in Acromegaly

Eva C. Coopmans; Ammar Muhammad; Aart J. van der Lely; Joseph A. M. J. L. Janssen; Sebastian J. C. M. M. Neggers

Disclosures

J Clin Endocrinol Metab. 2019;104(6):1978-1988. 

In This Article

Abstract and Introduction

Abstract

Context: Pasireotide long-acting release (LAR) is a somatostatin multireceptor ligand, and in the current consensus criteria pasireotide LAR is considered the second-line medical treatment for acromegaly. We present in this article our recommendations to define the position of pasireotide LAR in the treatment of acromegaly and provide recommendations for the management of pasireotide-induced hyperglycemia.

Evidence Acquisition: Our recommendations are based on our experiences with the pasireotide LAR and pegvisomant (PEGV) combination study and the available basic or clinical articles published in peer-reviewed international journals on pasireotide LAR and acromegaly.

Evidence Synthesis: In accordance with the current consensus criteria, we recommend pasireotide LAR monotherapy as a second-line therapy in young patients who show tumor growth during first-generation somatostatin receptor ligand (SRL) therapy and in patients who show tumor growth during PEGV therapy. In addition, we recommend pasireotide LAR monotherapy in patients with headache not responsive to first-generation SRL therapy and in patients who experience side effects or are intolerant to PEGV monotherapy. In contrast to the current consensus criteria, we recommend considering combination therapy with pasireotide LAR and PEGV as third-line treatment in patients without diabetes at low PEGV dosages (≤80 mg/week) and in patients with tumor growth or symptoms of active acromegaly during first-generation SRL and PEGV combination therapy. With respect to pasireotide-induced hyperglycemia, we recommend a more liberal strategy of blood glucose monitoring during pasireotide treatment.

Conclusions: In contrast to the current consensus criteria, we recommend a more reluctant use of pasireotide LAR therapy for the treatment of acromegaly.

Introduction

Acromegaly is a rare disease characterized by elevated levels of GH and insulin-like growth factor 1 (IGF-1), usually as a result of a GH-secreting pituitary tumor.[1] Multimodal treatment approaches such as surgery, medical therapy, and radiotherapy are used to treat active acromegaly. The current consensus on the goals of acromegaly treatment include normalization of IGF-1 levels, reduction of GH levels below 1.0 mg/L, decrease of tumor volume, and improvement of clinical symptoms.[2,3]

Transsphenoidal surgery is considered the first-line treatment of pituitary microadenomas and intrasellar macroadenomas.[4,5] Surgery is effective in the management of acromegaly, and in experienced centers biochemical remission rates of 80% can be achieved. However, most patients have macroadenomas, often with suprasellar extension. In these circumstances, the cure rates after surgery are much lower. Thus, a large proportion of patients with acromegaly will need additional treatment, which will be medical treatment in the first place. Radiotherapy is generally reserved as a third-line treatment option and is considered in patients with biochemically persistent disease or tumor growth despite surgery or medical therapy.[6,7] Recent improvements in medical treatment options have resulted in biochemical control of acromegaly in most patients. However, for patients whose disease is inadequately controlled or patients who experience side effects with currently available medical therapies, new treatment options are needed.

In 2014, pasireotide long-acting release (LAR) was approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with acromegaly for whom surgery is not an option or is not curative.[8,9] Pasireotide LAR is a somatostatin multireceptor ligand with a unique receptor binding profile. Compared with first-generation somatostatin receptor ligands (SRLs), which show the highest affinity to somatostatin receptor subtype 2 (SSTR2), pasireotide binds with higher affinity to SSTR5, followed by SSTR2, SSTR3, and SSTR1.[10] It has a slightly lower affinity to SSTR2 than first-generation SRLs.[10] Because of the broader binding profile, pasireotide LAR has been suggested to have greater clinical efficacy in acromegaly than first-generation SRLs.

In 2017, the Acromegaly Consensus Group provided detailed guidance and recommendations on pharmacological options for acromegaly treatment.[3] Medical treatment with first-generation SRLs, dopamine agonists, or the GH receptor antagonist pegvisomant (PEGV) was recommended for patients for whom surgery is not an option or is not curative. The recently published consensus criteria of Melmed et al.[3] addressed the position of pasireotide LAR in the treatment of acromegaly and recommended pasireotide LAR monotherapy as a second-line therapy.

The aim of this minireview is to discuss the present position of pasireotide LAR in the treatment of acromegaly. The recommendations presented in this article are based on recent clinical evidence of the efficacy and safety of pasireotide LAR combined with our own clinical experience treating patients with acromegaly with pasireotide LAR.[11,12] We also provide recommendations for monitoring and management of pasireotide-induced hyperglycemia, because this is a common adverse effect of the drug.

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