Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4378 - 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 3 double-blind placebo (PBO)-controlled TELESTAR and TELECAST studies

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Dieter Hörsch

Citation

Annals of Oncology (2018) 29 (suppl_8): viii467-viii478. 10.1093/annonc/mdy293

Authors

D. Hörsch1, R. Garcia-Carbonero2, J.W. Valle3, P. Perros4, S. Welin5, L. Keeber6, A. Houchard7, P. Lapuerta8

Author affiliations

  • 1 Department Of Gastroenterology/endocrinology, ENETS Center of Excellence, Zentralklinik Bad Berka, 99437 - Bad Berka/DE
  • 2 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 3 Department Of Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 4 Department Of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne/GB
  • 5 Department Of Endocrine Oncology, Uppsala University Hospital, Uppsala/SE
  • 6 Rare Diseases, Ipsen Ltd, SL1 3XE - Slough/GB
  • 7 Clinical Statistics, Ipsen Pharma France, 92100 - Boulogne-Billancourt/FR
  • 8 Clinical Development, Lexicon Pharmaceuticals, Princeton/US
More

Resources

Abstract 4378

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.

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).Table: 1314P

PBO tidTE 250 mg tidTE 500 mg tid
Number of LAN patients randomly allocatedn = 29n = 10n = 15
u5-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 (%) patients
Any 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)00
Deaths1 (3)00

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.

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.

Editorial Acknowledgement

Writing and editorial/submission support provided by Emma Leah, PhD (Ipsen); Tom Vizard, PhD, and Richard McDonald (Watermeadow Medical), funded 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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings