Real-world evidence of effectiveness and safety of pasireotide in the treatment of acromegaly: a systematic review and meta-analysis

Abstract

Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. This meta-analysis aimed to evaluate the real-world effectiveness and safety of PAS-LAR in patients with acromegaly resistant to first-generation somatostatin receptor ligands (fgSRL). A systematic literature search was conducted in PubMed and Web of Science for real-world studies on PAS-LAR in acromegaly published between 2014 and 2023. Random-effects meta-analyses were performed on biochemical control rates, tumor shrinkage, and metabolic parameters. Twelve studies comprising 409 patients were included. The pooled rate of insulin-like growth factor 1 (IGF-1) control was 57.9% [95% CI: 48.4-66.8] and the percentage of patients with tumor shrinkage was 33.3% [95%CI: 19.7-50.4]. Significant reductions were observed in growth hormone standardized mean difference (SMD) 0.6 ng/mL [95% CI: 0.3 to 1.0] and IGF-1 levels SMD 0.9 ULN [95% CI: 0.4 to 1.4]. However, as expected, a worsening in glucose metabolism was noted as an increase in fasting glucose SMD - 0.8 mg/dL [95% CI: -1.0 to -0.5, p < 0.01], glycated hemoglobin SMD - 0.5% [95% CI: -0.7 to -0.2]. and type 2 diabetes mellitus prevalence SMD - 11.5% (95% CI: -17.5 to -5.5). PAS-LAR demonstrated higher effectiveness in real-world settings, with over 60% of patients achieving IGF-1 control compared to the around 30% efficacy observed in clinical trials. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.

Keywords: Acromegaly; Effectiveness; Hyperglycemia; Pasireotide; Pituitary adenoma; Real world.

Fig. 1

Flowchart of literature eligibility assessment process. Illustrates the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram, detailing the process of study selection for the systematic review and meta-analysis. * Two studies by Chiloiro et al. were retained because, they report on different endpoints. One study was kept for general outcomes, while the other was included specifically for its data on carbohydrate metabolism, which was not available in the first study. This ensures that no duplication of results occurs, while maximizing the use of all relevant data

Fig. 2

Forrest plot including the five studies reporting GH levels before and after PAS-LAR treatment. This forest plot illustrates the standardized mean difference (SMD) in growth hormone (GH) levels before and after pasireotide treatment across the five studies. The random effects model shows a significant reduction in GH levels post-treatment, with an SMD 0.6ng/dL (95% CI: 0.3 to 1.0, p < 0.01). Moderate to high heterogeneity is indicated (I² = 66.8%, p = 0.02)

Fig. 3

Forrest plot changes in glucose levels (a), HbA1c (b), and diabetes prevalence (c) Following pasireotide LAR treatment. It provides a comprehensive overview of the impact of Pasireotide LAR treatment on glucose metabolism in acromegaly patients. The figure is divided into three sections: (a) Glucose Levels (mg/dL) - This section illustrates the changes in pre-treatment and post-treatment glucose levels across multiple studies. The standardized mean difference (SMD) indicates a significant increase in glucose levels post-treatment. (b) HbA1c Levels (%) - This section displays the changes in HbA1c levels before and after treatment. The SMD demonstrates a notable increase in HbA1c levels. (c) Diabetes Prevalence (%) - This section highlights the prevalence of diabetes before and after treatment. The analysis shows a significant increase in diabetes prevalence

Fig. 4

Meta-analysis of the proportion of acromegaly patients achieving IGF-1 control with pasireotide treatment forrest plot (a), a funnel plot (b), and a sensitivity analysis (c). It consists of three parts: a forest plot (a), a funnel plot (b), and a sensitivity analysis (c). (a) Forest Plot - This plot illustrates the proportion of acromegaly patients achieving IGF-1 control in each included study, alongside the pooled proportion estimates. (b) Funnel Plot - The funnel plot assesses the potential for publication bias among the studies. The symmetrical distribution of points suggests minimal publication bias, although some outliers indicate variability in reported IGF-1 control rates. (c) Sensitivity Analysis - This analysis evaluates the robustness of the overall proportion estimate by sequentially omitting each study. The consistent range confirm the stability of the pooled estimate despite significant heterogeneity

Fig. 5

Proportion of acromegaly patients achieving tumor volume shrinkage following pasireotide treatment. It presents a meta-analysis of the proportion of acromegaly patients who experienced clinically significant tumor volume reduction after treatment with PAS-LAR. (Panel a): Forest Plot - This section summarizes the individual study results and the pooled proportion estimates for tumor volume shrinkage. (Panel b): Funnel Plot - This panel assesses potential publication bias by plotting the logit-transformed proportions against their standard errors. The symmetrical distribution of points suggests minimal publication bias, though some asymmetry and outliers indicate variability in reported shrinkage rates. (Panel c): Sensitivity Analysis - This section demonstrates the stability of the overall proportion estimate by sequentially excluding each study. The pooled proportion remains consistent (35–45%) despite the exclusion of individual studies

Fig. 6

Sensitivity analysis of Pasireotide effectiveness on IGF-1 control (a) and tumor volume shrinkage (b) in Patients with and without prior radiotherapy. Figure 6 shows the sensitivity analysis comparing the effectiveness of pasireotide in achieving IGF-1 control (a) and tumor volume reduction (b) between patients with and without prior radiotherapy. The analysis highlights differences in heterogeneity and treatment response between the two groups