More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY

Abstract

Objective: To report the final long-term safety and efficacy analyses of patients with acromegaly treated with pegvisomant from the ACROSTUDY. Design: Global (15 countries), multicentre, non-interventional study (2004-2017). Methods: The complete ACROSTUDY cohort comprised patients with acromegaly, who were being treated with pegvisomant (PEGV) prior to the study or at enrolment. Main endpoints were long-term safety (comorbidities, adverse events [AEs], pituitary tumour volumes, liver tests) and efficacy (IGF-1 changes). Results: Patients (n = 2221) were treated with PEGV for a median of 9.3 years (range, 0-20.8 years) and followed up for a median of 7.4 years (range, 0-13.9 years). Before PEGV, 96.3% had received other acromegaly treatments (surgery/radiotherapy/medications). Before PEGV treatment, 87.2% of patients reported comorbidities. During ACROSTUDY, 5567 AEs were reported in 56.5% of patients and of these 613 were considered treatment-related (in 16.5% of patients) and led to drug withdrawal in 1.3%. Pituitary imaging showed a tumour size increase in 7.1% of patients; the majority (71.1%) reported no changes. Abnormal AST or ALT liver tests occurred in 3.2% of patients. IGF-1 normalization rate improved over time, increasing from 11.4% at PEGV start to 53.7% at year 1, and reaching 75.4% at year 10 with use of ≥30 mg PEGV/day in an increasing proportion of patients. Conclusion: This comprehensive review of the complete cohort in ACROSTUDY confirmed the overall favourable benefit-to-risk profile and high efficacy of PEGV as mono- and combination therapy in patients with an aggressive course/uncontrolled/active acromegaly requiring long-term medical therapy for control.

Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly

“…Despite our study was not being designed to provide data of efficacy of second line therapies, we found that at the follow-up last visit, the control of acromegaly was reached in 22 patients treated with m-Peg-V (66.7%), in 22 patients treated with c-Peg-V (63.9%) and in 25 patients treated with Pasireotide Lar (74.2%). These data are superimposable to those observed in previous series, as the reaching of acromegaly control is reported from 64% to 97% of patients treated with Peg-V in long term follow-up [24][25][26][27][28][29][30][31][32][33][34][35]. This magnitude in the percentage of patients who reached the control of acromegaly by second line therapies may be justified by the different study design (such as clinical trials, randomized or real life studies) and from the dosage of therapies.…”

Approach to the Patient With Treatment-resistant Acromegaly

“…The consensus statements ( 4 ) recommend a combination of first-generation SRL and PEGV in patients who remain uncontrolled with first-generation SRL and with impaired glucose tolerance and tumor concern. In contrast to the consensus statements, we recommend first-generation SRL and PEGV combination therapy as the second-line treatment of choice in nonresponders to first-generation SRL because it can lead to IGF-1 normalization in most patients ( 22 , 23 ). Although PEGV monotherapy does not reduce tumor size, combination therapy has the potential advantage that it may result in tumor size control or even tumor shrinkage in most patients ( 22 , 24 ).…”

Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY

“…The present investigation is based on the complete analysis set of ACROSTUDY, including data from 15 countries, collected between 2004 and December 2017, when ACROSTUDY was terminated [ 19 ]. Since some nations had enrolled a limited number of patients, we focused the analysis to data from the six top-recruiter countries, i.e., Germany, Italy, France, USA, Spain and the Netherlands.…”