Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period

Abstract

Background: The phase III, placebo‐controlled, randomized TELESTAR study evaluated efficacy and safety of telotristat ethyl (TE) in patients with diarrhea (≥4 bowel movements [BMs]/day) due to carcinoid syndrome (CS) inadequately controlled by somatostatin analogs (SSAs). TE, a tryptophan hydroxylase inhibitor, decreases peripheral serotonin. As add‐on treatment to SSAs, TE 250 mg and TE 500 mg 3x/day (tid) significantly reduced BM frequency (P < 0.001) compared with placebo over the 12‐week Double‐blind Treatment (DBT) period. AfterWeek 12, patients crossed over to a 36‐week Open‐label Extension (OLE) with TE 500 mg tid; data from the full 48 weeks are presented. Methods: Changes from baseline in BM frequency (monitored weekly), urinary 5‐hydroxyindoleacetic acid (u5‐HIAA; Weeks 18, 24, and 48), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30) score (Weeks 24 and 48), and safety during the OLE were evaluated. Results: Of 135 patients randomly assigned, 118 completed the DBT period; 115 patients subsequently entered (79 completed) the OLE. Of the 36 patients who discontinued the OLE, the most frequent reasons were adverse event (AE; 15 patients) and withdrawal of consent (9 patients). Treatment‐emergent AEs led 18 patients to discontinue TE, most commonly due to gastrointestinal disorder (6 patients). Reductions from baseline in BM frequency (~2 BMs/day) and u5‐HIAA (range, ‐20.0mg to ‐49.5 mg/24 hours) during the OLE were consistent with results of the DBT period and persisted through Week 48. Improvement in EORTC QLQ‐C30 diarrhea subscale scores relative to baseline (range, ‐18.8 to ‐30.6 points) was notable and persisted throughWeek 48. Crossover into the OLE was well tolerated. Treatment‐emergent AEs were mainly mild to moderate and occurred at similar rates as in the DBT period. Conclusion: Patients benefited from TE throughout the OLE, was well tolerated over 48 weeks, and showed efficacy consistent with previously reported data.