The safety and efficacy of telotristat ethyl (TE) in patients (pts) with metastatic neuroendocrine tumors (NETs) and carcinoid syndrome (CS) not adequately controlled with somatostatin analogs (SSAs) have been demonstrated. TE-treated pts showed significantly greater reductions in bowel movement (BM) frequency and more presented with durable response than placebo (PBO)-treated pts. These post-hoc analyses examined the relationship between improvements in symptoms and health-related quality of life (HRQoL) in pts who were durable responders (DRs; n = 48) and non-durable responders (NDRs; n = 87), irrespective of treatment group, in TELESTAR (NCT01677910).
Pts were randomized 1:1:1 to TE 250mg, 500mg, and PBO three times daily during the 12-week (wk) double-blind (DB) treatment period; durable response was predefined as a daily BM frequency reduction of ≥ 30% from baseline for ≥50% of the DB period. Clinical symptoms were assessed via daily records, HRQoL by the EORTC QLQ-C30 and QLQ-GINET21 questionnaires. The difference in arithmetic means and associated 95% CIs were used as a descriptive measure of group effects.
135 pts were randomized, 45 in each group. The mean difference [95% CI] in change from baseline between DRs and NDRs at Wk12 was (1.8 [-2.3, -1.2]) for daily BM frequency, (-1.2 [-1.6, -0.7]) for daily flushing, (-38.7 [-70.0, -7.3] mg/24 hrs) for u5-HIAA levels, (-1.2 [-1.8, -0.6]) for abdominal pain severity and (-0.3 [-0.4, -0.2]) for urgency to defecate. DRs showed meaningful and/or significant improvements in QLQ-C30 global health (8.1 [-0.3, 16.5]), summary score (4.9 [0.6, 9.2]), social functioning (5.1 [-4.7, 14.9]), nausea/vomiting (-7.5 [-15.4, 0.4]), pain (-16.0 [-27.0, -5.0]), dyspnea (-5.7 [-15.5, 4.1]), diarrhea (-14.7 [-26.5, -2.9]), and GINET21 gastrointestinal symptoms (-9.3 [-16.3, -2.2]) versus NDRs.
Durable response was associated with reductions in the symptoms and overall clinical burden of CS. DRs showed significant and/or meaningful improvements in global HRQoL, nausea, pain, diarrhea, and gastrointestinal symptoms.
Clinical trial identification
Legal entity responsible for the study
Lexicon Pharmaceuticals and Ipsen
M. Pavel: Consulting fees and honoaria from Ipsen, Lexicon Pharmaceuticals, Novartis, Pfizer. D. Cella: Consulting fees and research grants from Bayer, BMS, Ipsen, Novartis, Pfizer. J.L. Beaumont: Consulting fees from Novartis. F. Marteau, M. Feuilly, S. Gabriel, A. Houchard: Employee of Ipsen. J. Ramage: Speaker’s fees from Ipsen, Novartis, Pfizer; Research grants from IEL, Ipsen, Novartis, Pfizer. D. Hörsch: Consulting and/or honoraria and/or advisory boards from Ipsen, Lexicon Pharmaceuticals, Novartis, Pfizer; Research grants from Ipsen, Novartis, Pfizer. M.H. Kulke: Consulting fees from Ipsen, Lexicon Pharmaceuticals. All other authors have declared no conflicts of interest.