Efficacy of Lanreotide 120 mg Primary Therapy on Tumour Shrinkage and Ophthalmologic Symptoms in Acromegaly After 1 Month

Hamza Benderradji MD, PhD student; Elise Vernotte MD; Gustave Soto Ares MD; Jean Philippe Woillez MD, PhD; Arnaud Jannin MD, PhD student; Romain Perbet MD, PhD; Mélodie-Anne Karnoub MD; Benoît Soudan MD; Richard Assaker MD; Luc Buée PhD; Vincent Prevot PhD; Claude-Alain Maurage MD, PhD; Pascal Pigny MD, PhD; Marie-Christine Vantyghem MD, PhD; Emilie Merlen MD; Christine Cortet MD

Disclosures

Clin Endocrinol. 2022;97(1):52-63. 

In This Article

Abstract and Introduction

Abstract

Introduction: Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogues in somatotroph macroadenomas.

Objective: To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at 1 and 3 months on tumour shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromegaly.

Design and Patients: This single-centre retrospective study included 21 patients with de novo acromegaly resulting from pituitary macroadenoma, with optic chiasm compression (Grade ≤ 2) and/or cavernous sinus invasion, treated with a monthly injection of lanreotide 120 mg. Clinical, hormonal, ophthalmologic and magnetic resonance imaging scan evaluations were conducted after the first and the third months of treatment.

Results: Tumour volume reduction was more pronounced at 1 month; mean volume change: −31.4 ± 19.5%, p < .0001 than between the first and third month of treatment; mean volume reduction: −20.6 ± 13.4%, p = .0009. The mean volume change between baseline and the third month was − 46.4 ± 21.6, (p < .0001). A significant volume reduction (≥25%) was observed in 61.9% of individuals (13/21) at the first month. Among 14 individuals with optic chiasm compression and visual field defects, visual field normalization or improvement were observed in seven cases (50%), stabilization in four cases (28.5%), and mild worsening in three cases (21.4%) at 1 month. The decrease in growth hormone and IGF-1 serum values was significant at 1 month.

Conclusions: Primary treatment with lanreotide 120 mg in patients with somatotroph macroadenomas provides early significant tumour shrinkage with rapid improvement of visual symptoms at the end of the first month in 50% of patients.

Introduction

Current treatment guidelines for acromegaly recommend surgery as the primary therapy in most patients, except those with a high surgical risk, refuse surgery or have invasive, unresectable tumours. In these patients, primary medical treatment is an alternative to surgery.[1,2] Medical therapy has an essential role in the management of acromegaly, either in first-line treatment as an alternative to surgery or as an adjuvant therapy. First-generation long-acting somatostatin analogues are the first-line medical therapy in patients with acromegaly. Prospective studies have shown that 3−6 months of presurgical treatment with lanreotide or octreotide might improve the surgical cure rate in newly diagnosed patients with acromegaly at 3 and 6 months of follow-up; however, results are controversial and no advantage was demonstrated in long-term follow-up.[3–5]

Previous studies evaluating somatostatin analogues as first-line therapy have shown significant tumour volume reduction.[6–10] Some were compromised by limiting bias such as mixed treatment or variable doses, and heterogeneous populations (e.g., micro- and macroadenomas). A meta-analysis and a systematic review[11,12] concluded that first-line treatment with octreotide or lanreotide might produce tumour shrinkage in up to two-thirds of patients in the first year of treatment; in addition, more than 80% of patients undergoing tumour shrinkage on lanreotide had macroadenomas. Tumour shrinkage was more frequent in treatment-naive patients compared with those previously treated by radiotherapy, surgery, or drugs other than lanreotide.

A recent prospective study interestingly reported that primary treatment with lanreotide 120 mg, administered without dose titration, in patients with growth hormone (GH)-secreting macroadenomas provided early (at the end of the third month) and sustained reductions in tumour volume, GH and IGF-1 levels, and acromegalic symptoms up to 1 year of follow-up.[10]

However, no studies have reported the early efficacy of somatostatin analogues in reducing tumour volume and/or improving ophthalmologic symptoms, especially at the first month of treatment.

In a recent large international multicentre study, optic chiasm compression was observed in 17.8% (53/297) of patients with GH-secreting pituitary macroadenomas.[13] In cases of optic chiasm compression related to somatotroph macroadenomas, transsphenoidal surgery is usually proposed as first-line therapy, which allows removal of the pituitary tumour and relieves the optic chiasm compression since there are no data on the short-term antitumoral efficacy of somatostatin analogues in these patients. To clarify this issue, the current retrospective study aims to assess the efficacy on tumour shrinkage and ophthalmologic symptoms after 1 and 3 months of treatment with lanreotide 120 mg administered every 4 weeks in somatostatin analogue-naive patients without dose titration.

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