Association of weight change with telotristat ethyl in the treatment of carcinoid syndrome.

Abstract

e15692 Background: In the Phase 3 TELESTAR study, the oral tryptophan hydroxylase inhibitor telotristat ethyl (TE) significantly reduced bowel movement (BM) frequency compared with placebo (pbo) over a 12-week Double-blind Treatment (DBT) period in patients with carcinoid syndrome (CS). Weight loss has previously been associated with uncontrolled CS and may result in reduced survival, so it is important to examine weight changes in patients with neuroendocrine tumors (NETs). Methods: We conducted an analysis, prespecified in the statistical analysis plan, of the incidence of weight change of ≥3% at Week 12 in TELESTAR. Patients with metastatic NETs, CS, and ≥4 BMs per day were randomly assigned to receive pbo, TE 250 mg 3x/day (tid), or TE 500 mg tid for 12 weeks, in addition to somatostatin analog therapy. Results: There were 45 patients in each group. Mean baseline age was 63.5 years, with 5.8 BMs/day and mean body mass index 24.87 kg/m2. Weight gain ≥3% at Week 12 was observed in 2/39 (5.1%), 7/41 (17.1%), and 13/40 (32.5%) patients on pbo, TE 250 tid, and TE 500 mg tid, respectively. The Cochrane–Armitage test for trend in weight gain incidence across groups yielded p = 0.0017. Among the 20 patients with a ≥3% weight gain on TE, 10 patients experienced a reduction of at least 30% in BM frequency at Week 12 (maximum reduction 75%). Weight loss ≥3% at Week 12 was observed in 5 (12.8%), 4 (9.8%), and 6 (15.0%) patients on pbo, TE 250 tid, and TE 500 mg tid. Adverse events of vomiting, decreased appetite, cachexia, and performance status decreased were reported during the DBT period among those with weight loss but not those with weight gain. Conclusions: The incidence of weight gain was dose-related on TE and was greater than that on pbo. It was possibly related to a reduction in diarrhea severity, and it may be a relevant aspect of TE efficacy among patients with functioning metastatic NETs. Clinical trial information: NCT01677910.