Endocrine Abstracts

Background: The response to first-generation long-acting somatostatin analogues (LA-SSA) treatment in acromegaly depends on the expression of the somatostatin receptor (SSTR) subtypes. In contrast to octreotide and lanreotide which preferentially bind to SSTR2, pasireotide targets multiple SSTRs, with the highest binding affinity for SSTR5. It has previously been suggested that SSTR5 expression could predict the response to pasireotide LAR (PAS-LAR) treatment in acromegaly.

Aim: To assess whether the IGF-I response to LA-SSA monotherapy correlates with the IGF-I response to PAS-LAR treatment, and whether SSTR2 and SSTR5 expression correlate with response to PAS-LAR treatment in acromegaly.

Methods: We included 52 patients from a cohort of patients that initially received LA-SSA treatment, followed by LA-SSA and pegvisomant (PEGV) combination treatment and subsequently PAS-LAR treatment during the PAS-LAR and PEGV (PAPE) study. We excluded patients that had received radiotherapy and LA-SSA therapy ≤ 4 months. In 14 of 52 patients, somatotroph adenoma tissues samples were available for evaluation of SSTR2 and SSTR5 expression using a semiquantitative immunoreactivity score (IRS). The response to LA-SSA treatment was defined as IGF-I levels after ≥ 4 months LA-SSA monotherapy. The response to PAS-LAR treatment was based on the PAPE study and defined as IGF-I levels at 24 weeks and the percentage PEGV dose reduction at 48 weeks.

Results: The mean percentage IGF-I (x ULN) reduction was similar after LA-SSA monotherapy and after PAS-LAR treatment (resp. 32.1% and 30.0%) and IGF-l levels after both treatments were directly correlated (r=0.50, P=0.0002, n=52). The SSTR2 IRS was inversely correlated with IGF-I levels after PAS-LAR treatment at 24 weeks(r=0.63, P=0.016), but no correlation was observed with SSTR5 (r=−0.61, P=0.029, n=14). After exclusion of patients receiving LA-SSA pretreatment, SSTR2 IRS was correlated with the percentage PEGV dose reduction at 48 weeks after switching from LA-SSA/PEGV combination treatment to PAS-LAR treatment (r=0.70, P=0.035), while SSTR5 IRS showed no correlation (r=0.35, P=0.36).

Conclusion: In contrast to previous reports, SSTR5 expression does not predict the IGF-I response to PAS-LAR treatment, but appears to be mainly driven by SSTR2 expression.