Abstract 4162
Background
In the 16-wk double-blind (DB) phase of ELECT, LAN significantly reduced the need for short-acting octreotide (OCT) rescue medication for symptomatic control of CS in NET patients vs PBO (primary result). Here we present posthoc data on patient-reported symptoms during DB treatment.
Methods
ELECT consisted of 16-wk DB, 32-wk initial open-label, and long-term phases. Adults with histopathologically confirmed NET or NET of unknown location with liver metastases and history of CS (diarrhea and/or flushing) with/without prior somatostatin analog (SSA) use who provided informed consent were randomized to LAN 120 mg or PBO every 4 wks. Patients could administer short-acting OCT if needed and were instructed to record daily the frequency and severity of symptoms in a diary using Interactive Voice (Web) Response System for 1 month pre-randomization and throughout the DB phase. Analysis of covariance (ANCOVA) models were used for these analyses with baseline symptoms, prior SSA, and country as factors. Given the high variability of urinary 5-hydroxyindoleacetic acid (5HIAA), values were log transformed.
Results
115 patients were randomized (n = 59 LAN, n = 56 PBO). In the DB phase, percentages of days with severe or moderate/severe diarrhea and/or flushing compared to baseline were significantly reduced for LAN vs PBO (Table). The LAN group had a 35% greater decrease in logarithmic 5HIAA levels at wk 12 vs PBO (relative mean ratio 0.65; 95% CI: 0.40, 1.07). Treatment-emergent adverse events occurred in 53.4% of patients on LAN and 59.6% of patients on PBO.
Percentage days of diarrhea and/or flushing (ANCOVA, Intention-to-Treat Population)
| LAN (n = 59) | PBO (n = 56) | LS mean diff (LAN-PBO) (95% CI) | % reduction | P-value | |
|---|---|---|---|---|---|
| Moderate/Severe Diarrhea/Flushing | |||||
| LS Mean (SE), % | 23.4 (3.06) | 35.8 (3.12) | -12.4 (-20.73, -4.07) | 34.6 | 0.004 |
| Severe Diarrhea/Flushing | |||||
| LS Mean (SE), % | 3.9 (1.20) | 7.6 (1.23) | -3.8 (-7.01, -0.52) | 49.3 | 0.023 |
Conclusions
The observed improvement in patient-reported symptoms supports the efficacy of LAN in CS. These findings are in concert with the previously reported primary result of less rescue medication use with LAN vs PBO.
Clinical trial identification
EudraCT 2010-019066-92; NCT00774930 authors: on behalf of ELECT study investigators
Legal entity responsible for the study
Ipsen Biopharmaceuticals, Inc.
Funding
The study was funded by Ipsen Biopharmaceuticals, Inc.
Disclosure
E.M. Wolin: Consulting or Advisory Role – Celgene; Ipsen; Novartis; Pfizer; Research Funding – Ipsen (Inst); Novartis (Inst); Pfizer (Inst).
G.A. Fisher, Jr: Consulting—Ipsen; Research funding, Ipsen.
P.L. Kunz: Research funding from Genentech, Merck, Advanced Accelerator Applications, Lexicon, Oxigene; Advisor for Ipsen, Novartis.
N. Liyanage, S.P. Lowenthal, B. Mirakhur: Employee Ipsen Biopharmaceuticals, Inc.
A. Vinik: Consulting or Advisory Role – Isis Pharmaceuticals; Merck Co., Inc.; Neurometrix; Pamlab; Pfizer; Speakers' Bureau – Merck Co., Inc.; Pamlab; Research Funding – Daiichi Sankyo; Impeto Medical; Intarcia Therapeutics; Pfizer; Tercica; ViroMed.
All other authors have declared no conflicts of interest.