Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study

Abstract

Purpose PRIMARYS (NCT00690898) was a 48-week, open-label, phase 3b study, evaluating treatment with the somatostatin receptor ligand lanreotide autogel (stable dose: 120 mg/28 days) in treatment-naïve patients with growth hormone (GH)-secreting pituitary macroadenoma. This post hoc analysis aimed to evaluate factors predictive of long-term responses. Methods Potential predictive factors evaluated were: sex, age, and body mass index at baseline; and GH, insulin-like growth factor-1 (IGF-1), and tumor volume (TV) at baseline and week 12, using univariate regression analyses. Treatment responses were defined as hormonal control (GH ≤ 2.5 µg/L and age-and sex-normalized IGF-1), tight hormonal control (GH < 1.0 µg/L and normalized IGF-1), or ≥ 20% TV reduction (TVR). Receiver-operating-characteristic (ROC) curves were constructed using predictive factors significant in univariate analyses. Cut-off values for predicting treatment responses at 12 months were derived by maximizing the Youden index (J). Results At baseline, older age, female sex, and lower IGF-1 levels were associated with an increased probability of achieving long-term hormonal control. ROC area-under-the curve (AUC) values for hormonal control were high for week-12 GH and IGF-1 levels (0.87 and 0.93, respectively); associated cut-off values were 1.19 μg/L and 110% of the upper limit of normal (ULN), respectively. Results were similar for tight hormonal control (AUC values: 0.92 [GH] and 0.87 [IGF-1]; cut-off values: 1.11 μg/L and 125% ULN, respectively). AUC and J values associated with TVR were low. Conclusions The use of predictive factors at baseline and week 12 of treatment could inform clinical expectations of the long-term efficacy of lanreotide autogel.

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective

“…Furthermore, this finding is not at odds with previous studies describing an association between lower IGF-1 levels at baseline and a higher percentage of biochemical control after SRL treatment (21)(22)(23)(24)50). Indeed, although showing a lower relative reduction of hormone secretion, patients with lower baseline IGF-1 levels are (obviously) more likely to achieve the threshold set for biochemical control.…”

“…To date, a number of studies have investigated the potential role of clinical, radiological and molecular determinants able to predict the biochemical response to SRL treatment in acromegaly, although data are hardly comparable due to the high heterogeneity among the reported studies (e.g. prospective vs. retrospective design, various definitions of biochemical control, first-line therapy vs. adjuvant treatment) (20)(21)(22)(23)(24). The main clinical predictors of biochemical response to fg-SRL treatment identified so far are: lower baseline IGF-1 levels and older age at diagnosis (11,21,22).…”

“…prospective vs. retrospective design, various definitions of biochemical control, first-line therapy vs. adjuvant treatment) (20)(21)(22)(23)(24). The main clinical predictors of biochemical response to fg-SRL treatment identified so far are: lower baseline IGF-1 levels and older age at diagnosis (11,21,22). As for the radiological features, a T2-weighted hypointense signal of the pituitary lesion has been associated with a better response to SRL therapy in acromegaly patients (25)(26)(27)(28)(29).…”

A Pituitary Society update to acromegaly management guidelines

“…In the PRIMARYS study of lanreotide 120 mg in patients with treatment-naive macroadenomas, ≥ 20% tumor volume reduction was achieved in 54% at 12 weeks and in 63% at 48 weeks or the last post-baseline visit available [ 58 ]. Older age, female sex, and lower IGF-I levels at baseline were associated with increased probability of achieving long-term biochemical control, but tumor volume response at 12 weeks was not an accurate predictor of subsequent tumor volume control [ 59 ]. Further, patients with a hypointense tumor on T2 MRI showed greater reductions in IGF-I and were more likely to achieve tumor shrinkage [ 60 ].…”

Pasireotide in the Personalized Treatment of Acromegaly

“…Thereafter, two long-acting formulations of both octreotide (octreotide Long-Acting Release-LAR) and lanreotide (lanreotide autogel-ATG) were available, allowing monthly injections, a very convenient characteristic for the patient’s compliance. Besides reducing GH and IGF-1, they also provide a substantial tumor reduction effect that makes them very interesting for acromegaly treatment ( 29 – 32 ). Additionally, a new formulation of SRLs, which is allow oral administration of octreotide, has recently demonstrated its efficacy and safety in patient optimally controlled with the parenteral formulation, thus facilitating treatment compliance in those patients reluctant to receive monthly injections ( 33 )…”