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.

Keywords: Acromegaly; Baseline IGF-1; Growth hormone; Hormonal response; Predictive factors; Somatostatin receptor ligands.

Fig. 1

Proportions of patients achieving a hormonal control (defined as GH ≤ 2.5 µg/L and IGF-1 levels within normal ranges at LVA) and b tight hormonal control (defined as GH < 1.0 µg/L and IGF-1 levels within normal ranges at LVA), at LVA according to baseline GH and IGF-1 levels. GH growth hormone, IGF-1 insulin-like growth factor-1, LVA last post-baseline value available. Patients with baseline IGF-1 levels between 380 and < 740% ULN were grouped together. Of the two patients who achieved tight hormonal control at LVA, one patient had IGF-1 levels between 460 and 500% ULN, and the other between 540 and 580% ULN. Data are from the intention-to-treat population for patients with LVA data (n = 88)

Fig. 2

Proportions of patients achieving TV responder status at LVA according to baseline TV. TV tumor volume, LVA last post-baseline value available. Data are from the intention-to-treat population for patients with LVA data (n = 89). TV responder status was defined as ≤ 20% reduction in TV

Fig. 3

ROC curves drawn for the calculation of week-12 cut-off values for predicting hormonal control and TV responder status at LVA when a hormonal control is defined as GH ≤ 2.5 µg/L and IGF-1 levels within normal ranges at LVA, b tight hormonal control is defined as GH < 1.0 µg/L and IGF-1 levels within normal ranges at LVA, and c TV responder status is defined as ≤ 20% reduction in TV at LVA. GH growth hormone, IGF-1 insulin-like growth factor-1, LVA last post-baseline value available, ROC receiver operating characteristic, TV tumor volume, ULN upper limit of normal. Data are from the intention-to-treat population for patients with LVA data (n = 88)