Evidence for the use of telotristat ethyl for refractory carcinoid syndrome comes from two companion phase III double-blind, international randomised controlled studies, the TELESTAR and TELECAST studies.rr
Between January 2013 and March 2015, 135 patients with carcinoid syndrome refractory to SSA therapy and experiencing ≥ 4 bowel movements (BMs) per day were randomised 1:1:1 to receive placebo, telotristat ethyl 250 mg or telotristat ethyl 500 mg orally three times a day for 12 weeks. Patients continued to receive their baseline SSA therapy during this period. There was a 36 week open-label extension, where 115 patients subsequently received telotristat ethyl 500 mg.r
The primary endpoint was mean change from baseline BM frequency. Secondary endpoints included change from baseline in urinary 5-HIAA, the number of daily flushing episodes, and abdominal pain severity.
The companion TELECAST study included 76 patients experiencing < 4 BMs per day on SSA therapy (or ≥ 1 symptom or ≥ 4 BMs per day if not on SSAs).r
The primary endpoints were percentage change from baseline in urinary 5-HIAA level and incidence of treatment-emergent adverse events.
After 12 weeks of treatment, daily BMs had reduced significantly more with telotristat ethyl (1.7 fewer with 250 mg dose and 2.1 fewer with 500 mg dose) compared to placebo (0.9 fewer). More patients had a response to treatment in the telotristat ethyl groups (defined as at least a 30% reduction in BMs from baseline). The telostristat ethyl groups were associated with a statistically significant reduction in urinary 5-HIAA level and improved health-related quality of life compared with placebo. There were no statistically significant differences between groups in the small number of patients experiencing flushing and abdominal pain.r
Change from baseline in frequency of bowel movementsr
©J Clin Oncol 2017
After 12 weeks of treatment, the urinary 5-HIAA levels had increased in the placebo group and reduced significantly in the two telotristat ethyl groups.r
Patients in the telotristat ethyl groups had a higher incidence of dose-related nausea (31% in the 500 mg group, compared to 13% in the 250 mg group and 11% in the placebo group). Dose-related increases in hepatic enzymes, particularly GGT, were observed in both telotristat ethyl groups. In the open-label extension, depression was more common with the higher dose of telotristat ethyl.r
©J Clin Oncol 2017