1314P - Efficacy and safety of telotristat ethyl (TE) in combination with lanreotide (LAN) in patients with a neuroendocrine tumour and carcinoid syndrome (CS) diarrhoea (CSD): Meta-analysis of phase III double-blind placebo (PBO)-controlled TELESTAR and TELECAST studies

Abstract

Background: LAN 120 mg, a somatostatin analogue (SSA), is approved in the EU and recently in the USA for CS. In two phase 3 trials in CS, TE 250 mg or 500 mg three-times daily (tid) combined with SSA therapy (LAN or octreotide) demonstrated reduced bowel movement (BM) frequency and urinary 5-hydroxyindole acetic acid (u5-HIAA) levels vs. PBO. TE 250 mg is approved by the FDA and EMA for CSD inadequately controlled by SSAs. This post hoc meta-analysis used patient-level data from the two phase 3 studies to further examine the efficacy and safety of TE + LAN.Table: 1314PPBO tidTE 250 mg tidTE 500 mg tidNumber of LAN patients randomly allocatedn = 29n = 10n = 15u5-HIAA (mg/24 hour)Patients with levels > upper limit of normal (at randomization): n (%)15 (51.7)6 (60.0)9 (60.0)Baseline: median [95% CI]24.9 [12.2; 80.9]57.6 [12.9; 159.8]31.0 [19.0; 259.2]Week-12 change from baseline: median [95% CI]1.6 [–6.7; 5.0]–12.4 [–86.4; 77.2]–24.6 [–134.6; –10.0]BMs/day: median [95% CI]Baseline3.5 [2.4; 4.4]3.1 [1.3; 5.6]5.3 [3.6; 6.1]Week-12 change from baseline–0.2 [–1.1; 0.2]–0.9 [–2.6; –0.0]–1.29 [–3.3; –0.0]Flushing (counts/day): median [95% CI]Baseline3.5 [1.5; 5.1]2.8 [0.5; 4.9]2.9 [0.8; 4.3]Week-12 change from baseline0.00 [–1.1; 0.4]–0.5 [–1.2; 0.7]–0.5 [–2.0; 0.4]Safety: n (%) patientsAny AE26 (90)9 (90)14 (93)Treatment-related AEs8 (28)6 (60)12 (80)Serious AEs3 (10)1 (10)4 (27)Treatment-related serious AEs1 (3)00Deaths1 (3)00 Open table in a new tab Methods: In the TELESTAR (NCT01677910) and TELECAST (NCT02063659) studies, patients using and continuing stable-dose SSAs were randomly assigned 1:1:1 to PBO, TE 250 mg or TE 500 mg tid for a 12-week double-blind (DB) period. Here, only data for patients using LAN during the run-in periods were included. Endpoints included descriptive changes from baseline in 24-hour u5-HIAA, BMs/day, flushing episodes and incidence of adverse events (AEs). Results: Of 211 patients in the studies, 54 receiving LAN were included in the analysis (44% women, mean [SD] age 61.8 [10.5] years, mean [SD] BMI 25.7 [5.0] kg/m2; 34 [63%] used LAN 4-weekly, 20 [37%] used LAN 3-weekly). One patient received octreotide instead of LAN during the DB period. Randomization of this cohort is shown with efficacy and safety data in the table. Conclusions: Changes from baseline in u5-HIAA, BMs and flushing suggest a trend towards meaningful efficacy of TE + LAN in CSD, in a population with moderately elevated baseline BM frequency. The combination TE + LAN was generally well tolerated. No power calculation was performed for this exploratory post hoc analysis; imbalanced groups and low patient numbers preclude any formal comparison with PBO. Evaluation of this TE + LAN regimen as first-line therapy in patients with CSD may be warranted. Clinical trial identification: TELESTAR: NCT01677910 TELECAST: NCT02063659. Editorial acknowledgement: Writing and editorial/submission support provided by Emma Leah, PhD (Ipsen); Tom Vizard, PhD, and Richard McDonald (Watermeadow Medical), funded by Ipsen. Legal entity responsible for the study: Lexicon Pharmaceuticals Funding: The TELESTAR and TELECAST studies were sponsored by Lexicon Pharmaceuticals. This analysis was sponsored by Ipsen. Disclosure: D. Hörsch: Consultant: Ipsen, Lexicon, Novartis, Pfizer; Research investigator: Ipsen, Lexicon, Novartis, Pfizer; Speaker’s bureau: Ipsen, Lexicon, Novartis, Pfizer. R. Garcia-Carbonero: Honoraria: AAA, Ipsen, Novartis, Pfizer; Consultant: AAA, Ipsen, Novartis, Pfizer; Grant recipient: Pfizer; Research investigator: Ipsen, Novartis, Pfizer. J.W. Valle: Honoraria: Ipsen. Consultant: Ipsen; Grant recipient: Ipsen; Research investigator: Ipsen. Speaker's bureau: Ipsen. S. Welin: Honoraria: Ipsen, Novartis. L. Keeber: Employee: Ipsen. A. Houchard: Grant recipient, Employee, Stock owner: Ipsen. P. Lapuerta: Employee, Stock owner: Lexicon Pharmaceuticals. All other authors have declared no conflicts of interest.