Introduction: Somatostatin analogues (SSAs) are the mainstay of treatment for carcinoid syndrome (CS)-related symptoms. Controversy still exists regarding the extent of the efficacy of this intervention. The purpose of the systematic review and meta-analysis was to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of SSAs (lanreotide, octreotide, pasireotide) in patients with CS. Due to lack of uniformity and established criteria for defining the response to treatment, definition of PR and CR was based on ad hoc criteria provided in individual studies.
Methods: A systematic electronic literature search was conducted in major healthcare databases to identify eligible studies complemented by an ancillary search in the references of the retrieved studies. Any clinical trial reporting data on the efficacy of SSAs in at least 10 adult participants with minimum follow-up of three months were considered eligible for the meta-analysis. A subset of studies, in which outcomes were reported as PR or CR were considered for meta-analysis of binomial data.
Results: A total of 25 studies (published between 19942018 involving a total sample size of 1517 patients with CS) finally fulfilled the inclusion criteria of the systematic review and 11 studies reported extractable outcomes (PR or CR) were considered for quantitative synthesis. Significant heterogeneity was noted with regards to study design, definition of the primary outcome, follow-up, specific formulation, total dose administration, location of the primary tumour and extent of the disease. The pooled percentage of patients with PR or CR for diarrhoea was estimated 0.40 (11 studies, 95% confidence interval (CI): 0.230.58, I2 test-for-heterogeneity=97.5%). Subgroup analyses on the basis of specific drug provided no evidence of a differential response. For lanreotide and octreotide, the pooled percentage of patients with PR or CR was calculated 0.38 (95CI%: 0.230.53) and 0.51 (95CI%: 0.190.83), respectively. The pooled percentage of patients for flushing with PR or CR was estimated 0.40 (11 studies 95%CI: 0.250.55, I2=93.4%). No evidence of a significant differential response in the control of flushing was noted (pooled percentage of patients with PR or CR for lanreotide was 0.35 (0.150.54) and for octreotide 0.52 (0.3964)). Relative paucity of data prevented the calculation of pasireotide-specific outcomes.
Conclusion: This systematic review and meta-analysis provides preliminary estimate of a 40% overall reduction of symptoms of CS associated with SSAs administration. However, significant heterogeneity was detected, possibly reflecting differences in clinical course and manifestation of the disease as well as in outcome definition.
18 - 21 May 2019
European Society of Endocrinology