Objective: In a completed phase III study (C2305, Clinicaltrials.gov identifier: NCT00600886), the reported rate of biochemical control with octreotide long-acting release (LAR) was lower than rates historically reported in patients pretreated and/or selected for response with somatostatin analogue (SSA) therapy. To assess whether lower efficacy rates of octreotide LAR in C2305 were influenced by study design, a systematic review of the literature was performed to evaluate response rates in previously published studies in acromegaly with similar design characteristics.
Methods: PubMed was used to search for English-language clinical studies of acromegaly published through May 2014. Prospective studies of medically naïve patients (≥20) treated with SSAs for ≤12 months that reported efficacy rates using composite endpoint measures (growth hormone [GH] and insulin-like growth factor 1 [IGF-1]) were included. Two separate authors independently screened abstracts and full-length articles of each study to determine eligibility. All authors met to review and reach consensus when primary reviewers disagreed on the inclusion or exclusion of specific studies.
Results: A total of 9 studies (N = 354 patients) were identified, with reported mean efficacy rates of 31% (range, 20-54%). Of note, reported mean efficacy rates were lower in studies enrolling patients naïve to any form of treatment (surgery, medical, and/or radiation) than in studies that enrolled only medically naïve patients. A limitation of this analysis was that inclusion criteria restricted the number of studies analyzed.
Conclusion: Interpretation of biochemical response rates with SSAs is critically dependent on the context of the study and should be evaluated across clinical trials with similar study design characteristics.