TY - JOUR
T1 - Relationship Between Symptoms and Health-related Quality-of-life Benefits in Patients With Carcinoid Syndrome
T2 - Post Hoc Analyses From TELESTAR
AU - Cella, David
AU - Beaumont, Jennifer L.
AU - Hudgens, Stacie
AU - Marteau, Florence
AU - Feuilly, Marion
AU - Houchard, Aude
AU - Lapuerta, Pablo
AU - Ramage, John
AU - Pavel, Marianne
AU - Hörsch, Dieter
AU - Kulke, Matthew H.
N1 - Funding Information:
These analyses and costs for the development of this manuscript, including medical writing support, were funded by Ipsen Pharma (Boulogne-Billancourt, France). The study was sponsored by Lexicon Pharmaceuticals (The Woodlands, TX, USA).
Funding Information:
Dieter Hörsch: Consulting and/or honoraria and/or advisory boards from Ipsen, Lexicon Pharmaceuticals, Novartis, Pfizer; Research grants from Ipsen, Novartis, Pfizer.
Funding Information:
David Cella: Consulting fees and research grants from Bayer, Bristol-Myers Squibb, Ipsen, Novartis, Pfizer.
Funding Information:
John Ramage: Speaker’s fees from Ipsen, Novartis, Pfizer; Research grants from IEL, Ipsen, Novartis, Pfizer.
Funding Information:
The authors thank the patients and investigators for participating in the study. The authors acknowledge Lisa Wulund, PhD, and Amelia Frizell-Armitage, PhD (Costello Medical, Cambridge, UK), for medical writing support and editorial assistance in the preparation of the manuscript for publication, based on the authors’ input and direction with funding from Ipsen Pharma (Boulogne-Billancourt, France).
Publisher Copyright:
© 2018 The Authors
PY - 2018/12
Y1 - 2018/12
N2 - Purpose: Patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS) may experience chronic, recurring symptoms despite somatostatin analogue therapy. Little is known about the relationship between bowel movement (BM) frequency, patient-reported symptoms and health-related quality of life (QoL). Data from the TELESTAR study were used in exploratory, post hoc analyses to understand the relationship between durable reductions in BM frequency, symptom relief, and health-related QoL. Methods: Patients with metastatic neuroendocrine tumors and CS in the Phase III TELESTAR study were randomized (1:1:1) to receive telotristat ethyl (TE) 250 mg, TE 500 mg, or placebo three times daily (TID) during a 12-week double-blind treatment period (DBTP). All patients received TE 500 mg TID in an open-label extension (OLE) to Week 48. Durable response was predefined. Analyses compared durable responders (DRs) and non–durable responders (NDRs), irrespective of treatment group, at Weeks 12, 24, and 48. Findings: At the start of the DBTP, 135 patients were randomized, 45 patients each to TE 250 mg, TE 500 mg, and placebo. After the 12-week DBTP, 48 of 135 patients were DRs (TE 250 mg, n = 20; TE 500 mg, n = 19; placebo, n = 9). Of the 115 patients who entered the OLE, 35 were DRs initially randomized to TE 250 mg (n = 18) or 500 mg (n = 17), 29 of whom maintained a durable response throughout the OLE. Of the 71 DBTP-NDRs (inclusive of patients initially randomized to placebo), 28 became OLE-DRs. There were 29 NDRs initially randomized to placebo who entered the OLE, 16 of whom became DRs when switched to TE 500 mg. DRs during the DBTP had greater symptom improvements in the DBTP; these improvements continued over the OLE. DBTP-DRs also maintained more meaningful QoL improvements in EORTC QLQ-C30 global health status, nausea and vomiting, pain, diarrhea, and EORTC QLQ-GINET21 gastrointestinal symptoms over the DBTP and OLE periods than DBTP-NDRs. Implications: These results suggest that sustained improvements in BM frequency in patients with CS may have multifaceted, long-term effects on a patient's well-being. ClinicalTrials.gov identifiers: NCT01677910.
AB - Purpose: Patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS) may experience chronic, recurring symptoms despite somatostatin analogue therapy. Little is known about the relationship between bowel movement (BM) frequency, patient-reported symptoms and health-related quality of life (QoL). Data from the TELESTAR study were used in exploratory, post hoc analyses to understand the relationship between durable reductions in BM frequency, symptom relief, and health-related QoL. Methods: Patients with metastatic neuroendocrine tumors and CS in the Phase III TELESTAR study were randomized (1:1:1) to receive telotristat ethyl (TE) 250 mg, TE 500 mg, or placebo three times daily (TID) during a 12-week double-blind treatment period (DBTP). All patients received TE 500 mg TID in an open-label extension (OLE) to Week 48. Durable response was predefined. Analyses compared durable responders (DRs) and non–durable responders (NDRs), irrespective of treatment group, at Weeks 12, 24, and 48. Findings: At the start of the DBTP, 135 patients were randomized, 45 patients each to TE 250 mg, TE 500 mg, and placebo. After the 12-week DBTP, 48 of 135 patients were DRs (TE 250 mg, n = 20; TE 500 mg, n = 19; placebo, n = 9). Of the 115 patients who entered the OLE, 35 were DRs initially randomized to TE 250 mg (n = 18) or 500 mg (n = 17), 29 of whom maintained a durable response throughout the OLE. Of the 71 DBTP-NDRs (inclusive of patients initially randomized to placebo), 28 became OLE-DRs. There were 29 NDRs initially randomized to placebo who entered the OLE, 16 of whom became DRs when switched to TE 500 mg. DRs during the DBTP had greater symptom improvements in the DBTP; these improvements continued over the OLE. DBTP-DRs also maintained more meaningful QoL improvements in EORTC QLQ-C30 global health status, nausea and vomiting, pain, diarrhea, and EORTC QLQ-GINET21 gastrointestinal symptoms over the DBTP and OLE periods than DBTP-NDRs. Implications: These results suggest that sustained improvements in BM frequency in patients with CS may have multifaceted, long-term effects on a patient's well-being. ClinicalTrials.gov identifiers: NCT01677910.
KW - carcinoid syndrome
KW - health-related quality of life
KW - neuroendocrine tumors
KW - rare diseases
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UR - http://www.scopus.com/inward/citedby.url?scp=85057054167&partnerID=8YFLogxK
U2 - 10.1016/j.clinthera.2018.10.008
DO - 10.1016/j.clinthera.2018.10.008
M3 - Article
C2 - 30477789
AN - SCOPUS:85057054167
SN - 0149-2918
VL - 40
SP - 2006-2020.e2
JO - Clinical Therapeutics
JF - Clinical Therapeutics
IS - 12
ER -
