Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly

Abstract

ContextThe somatostatin analogues octreotide LAR and lanreotide Autogel have been evaluated for the treatment of acromegaly in numerous clinical trials, with considerable heterogeneity in reported biochemical response rates. This review examines and attempts to account for these differences in response rates reported in the literature.Evidence acquisitionPubMed was searched for English-language studies of a minimum duration of 24 weeks that evaluated ≥10 patients with acromegaly treated with octreotide LAR or lanreotide Autogel from 1990 to March 2015 and reported GH and/or IGF-1 data as the primary objective of the study.Evidence synthesisOf the 190 clinical trials found, 18 octreotide LAR and 15 lanreotide Autogel studies fulfilled the criteria for analysis. It is evident from the protocols of these studies that multiple factors are capable of impacting on reported response rates. Prospective studies reporting an intention-to-treat analysis that evaluated medically naïve patients and used the composite endpoint of both GH and IGF-1 control were associated with lower response rates. The use of non-composite biochemical control endpoints, heterogeneous patient populations, analyses that exclude treatment non-responders, assay variability and prior responsiveness to medical therapy are just a few of the factors identified that likely contribute to higher success rates.ConclusionsThe wide range of reported response rates with somatostatin analogues may be confusing and could lead to misinterpretation by both the patient and the physician in certain situations. Understanding the factors that potentially drive the variation in response rates should allow clinicians to better gauge treatment expectations in specific patients.

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

“…Clinical data supporting efficacy and safety of first-generation SSAs, long-acting octreotide [21] and lanreotide Autogel [22], in Japanese patients with acromegaly have previously been reported. In most of the studies, the response rate in patients treated with first-generation SSAs ranges from 17% to 41% [2,[23][24][25]. In a retrospective study, pegvisomant monotherapy showed efficacy with sustained IGF-1 normalization in Japanese patients with acromegaly; however, there was no effect on GH reduction and tumor shrinkage, and safety concerns like liver toxicity were observed [26], which is consistent with the known profile of pegvisomant.…”

Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control

“…8,14 However, many patients fail to achieve biochemical control with somatostatin analogues. 15 Pegvisomant is useful in patients who are inadequately controlled by somatostatin analogues, A Β Figure 4. Pasireotide suppressed GH (A) and IGF-1 (B) in patient 2 resistant to multiple treatment regimens.…”

A Consensus Statement on acromegaly therapeutic outcomes

“…Biochemical control rates of approximately 55% have been reported with the first-generation SRLs octreotide and lanretotide 60 ; however, data from rigorously conducted trials using currently available long-acting formulations show lower rates of 25-45% 16,17,19,61 (MQ). As patient selection bias, initial IGF1 levels, previous surgery, adverse effects and treatment compliance can all impact the likelihood of achieving biochemical control, in practice, biochemical response to first-generation SRLs is likely to be higher than that observed in trials published in the past 10 years but lower than in earlier trials (LQ) 62 . Octreotide long-acting release (LAR) is administered once monthly by intramuscular injection; lanreotide autogel is administered once monthly subcutaneously by the patient, their caregiver or a health-care provider.…”