Evaluation of disease-specific and functional symptom items on carcinoid tumor patients treated with telotristat ethyl.

Abstract

427 Background: Within the pivotal, phase III TELESTAR trial, telotristat ethyl significantly reduced bowel movement (BM) frequency compared to placebo ( P < 0.001) (NCT01677910). Assessing patient-related outcomes can help understand the impact of changes in BM frequency on patient lives. An analysis was done to determine whether individual items on patient-reported outcome measures show relevant patterns over the course of treatment for patients with carcinoid syndrome (CS). Methods: The TELESTAR study was a phase III, double-blind, parallel-group, randomized, placebo-controlled study comparing placebo (PBO) to telotristat ethyl (TE) in 135 patients with Carcinoid Syndrome (CS). Clinical quality of life (QoL) measurements included the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and European Organisation for Research and Treatment of Cancer (EORTC) GI.NET21 scales. Analyses on identified individual gastrointestinal (GI) symptom and role function items were conducted using longitudinal generalized estimation equations (GEE; reference=PBO) to characterize the likelihood of a 1-grade categorical improvement (e.g., improvement by one category on the verbal response scale). Forest plots of odds ratios (OR) and associated confidence intervals (CI) on individual items are presented. Results: At week 12, the likelihood of patients experiencing a 1-grade improvement on most GI symptoms were equivalent (OR approx. 1.0). The highest odds ratios observed with TE were for improvement in diarrhea (OR=1.86, CI=0.848-4.090) and a reduction in weight bother (OR=2.95, CI=0.713-12.199), in parallel to TELESTAR results for bowel movement frequency reduction and weight gain. Interference with daily activities (IADL) and limitations in doing work demonstrated similar outcomes (IADL OR=1.63, CI=0.617,4.288; Work OR=1.97, CI=0.722,5.376). Conclusions: The overall pattern of item level change on telotristat suggested clinical relevance for bowel movement frequency reduction and weight gain, and it was consistent with symptomatic and functional benefit in CS. Clinical trial information: NCT01677910.