Telotristat Etiprate Shows Clinical Benefit in Treating Carcinoid Syndrome in Cancer Patients When Added to Standard of Care
Lexicon Pharmaceuticals, Inc's telotristat etiprate was shown to have clinical benefit in treating carcinoid syndrome in cancer patients not adequately controlled by long-acting somatostatin analog therapy, the current standard of care, according to data from the phase III TELESTAR study presented at the 2015 European Cancer Congress in Vienna, Austria (Abstract 37LBA).
Telotristat etiprate met the study's primary endpoint with clinically meaningful reductions in bowel movement frequency in patients whose condition was not adequately controlled by somatostatin analog therapy. Carcinoid syndrome is characterized by frequent and debilitating diarrhea, as well as by facial flushing, abdominal pain, heart valve damage, and other serious consequences.
“We are pleased with the efficacy and safety results of telotristat etiprate and also with the durability of the response shown in this study,” said Lexicon Executive Vice President and Chief Medical Officer Pablo Lapuerta, MD. “The data also support that the compound is acting directly on the cause of carcinoid syndrome, by reducing serotonin production within tumor cells.”
“Telotristat etiprate represents a novel approach by specifically inhibiting serotonin synthesis and, as such, is a promising potential new treatment for patients whose lives can be significantly impacted by this debilitating condition,” said TELESTAR primary investigator Matthew H. Kulke, MD, Director, Program in Neuroendocrine and Carcinoid Tumors and Senior Physician, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. “These results are exciting from both an efficacy and safety perspective for carcinoid syndrome patients.”
“Carcinoid syndrome has a significant impact on the lives of patients who already have been battling metastatic cancer,” said Maryann Wahmann, Founder and President of the Neuroendocrine Cancer Awareness Network. “These patients can live for many years with their cancer, yet the symptoms of carcinoid syndrome are what frequently limit their lives and restrict their activities every single day. So there is a tremendous need for effective new treatment options.”
TELESTAR Results
The double blind, phase III study enrolled 135 patients with carcinoid syndrome that was not adequately controlled on somatostatin analog therapy. The three-arm study evaluated two doses of oral telotristat etiprate—250 mg and 500 mg, each taken 3 times daily—against placebo over a 12-week period and measured the reduction from baseline in the average number of daily bowel movements. Patients in both the treatment and placebo arms continued their somatostatin analog therapy throughout the study.
Data show that patients who added telotristat etiprate to somatostatin analog therapy at both the 250-mg and 500-mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (P < .001), meeting the study's primary endpoint.
Patients who received 250 mg of telotristat etiprate experienced a reduction of 1.71 bowel movements (29%) in the average number of daily bowel movements during the final week of the study compared to baseline, and those in the 500-mg arm experienced a reduction of 2.11 bowel movements (35%); the placebo group showed a reduction of 0.87 bowel movements (17%).
Durable Responses
A substantially greater proportion of patients on telotristat etiprate achieved a durable response (44% and 42% in the 250-mg and 500-mg arms, respectively), defined as at least a 30% reduction in daily bowel movements over at least half the days of the study period, as compared to 20% response on placebo (P < .02).
The mean change in urinary 5-HIAA—the main metabolite of serotonin—from baseline to week 12 was a reduction of 40 mg/24 hours in the 250-mg arm and 58 mg/24 hours in the 500-mg arm vs an increase of 11 mg/24 hours in the placebo group (P < .001). Baseline urinary 5-HIAA levels were 93 mg/24 hours in the 250-mg arm, 90 mg/24 hours in the 500-mg arm, and 81 mg/24 hours in the placebo group.
Patients who received telotristat etiprate also experienced a lower frequency of flushing episodes and less intense abdominal pain compared to placebo, though these differences did not reach statistical significance.
Treatment with telotristat etiprate was generally well tolerated during the double-blind treatment period. The proportions of patients with treatment-emergent adverse events were 82% in the 250-mg arm, 93% in the 500-mg arm, and 87% in the placebo group during the 12-week study period. The proportions of patients who discontinued treatment due to adverse events in both the 250-mg and 500-mg arms were 7% as compared to 13% in the placebo group.
The tolerability profile of the telotristat etiprate 250-mg dose appeared similar to placebo and somewhat better than the 500-mg dose in terms of gastrointestinal discomfort and mood. There were six events of patients experiencing mild-to-moderate nausea in the 250-mg arm, 13 in the 500-mg arm, and five in the placebo group. There were two events of depression or depressed mood in the 250-mg arm, eight in the 500-mg arm, and three in the placebo group. There were no discontinuations of treatment due to nausea, depression, or depressed mood in the 250-mg and 500-mg arms during the 12-week study period.
Novel Approach
Telotristat etiprate is the first investigational drug in clinical studies to target tryptophan hydroxylase, an enzyme that triggers the excess serotonin production within mNET cells that leads to carcinoid syndrome. While existing treatments for carcinoid syndrome work to reduce the release of serotonin outside tumor cells, telotristat etiprate works at the source to reduce serotonin production within the tumor cells. By specifically inhibiting serotonin production, telotristat etiprate seeks to control this important driver of carcinoid syndrome and, in turn, provide patients with more control over their disease.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
