Telotristat Ethyl Shows Promise in Managing Weight Loss for Metastatic Pancreatic Cancer Patients

New findings from a phase 2 clinical trial suggest that telotristat ethyl, when combined with standard chemotherapy, may offer a solution for weight management in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who experience significant weight loss. The results were presented at the 2025 ASCO Gastrointestinal Cancers Symposium.

Weight Stabilization Results

The study enrolled 22 patients divided into two groups based on their weight loss status. Group 1, comprising 14 patients who had lost at least 10% of their body weight, received a combination of gemcitabine and nab-paclitaxel chemotherapy plus telotristat ethyl (250mg three times daily). Group 2, with 8 patients who had lost less than 10% of their body weight, received chemotherapy alone.

Over a three-month period, Group 1 showed promising results with a mean weight change of -1.6% (90% CI, -6.7 to 3.4; P = .0595), compared to -4.4% (90% CI, -9.4 to -1.7; P = .5274) in Group 2. These findings suggest that telotristat ethyl may help stabilize weight in patients experiencing significant weight loss.

Impact on Serotonin Levels and Survival

The study monitored serontonin levels monthly, revealing significant reductions in both groups. At three months, Group 1 showed a median serotonin level decrease of 37.8% (IQR: -59.1 to -13; P = .064), while Group 2 experienced a 42.6% reduction (IQR: -57.8 to -29.9; P = .016).

Median overall survival reached 10.7 months (95% CI, 5.4-16.9) for Group 1 and 12.2 months (95% CI, 6.1-21.4) for Group 2 (HR = 1.41; 95% CI, 0.57-3.52; P = .46).

Safety and Tolerability

The safety profile of the combination therapy proved manageable, with adverse events consistent with known profiles of both the chemotherapy regimen and telotristat ethyl. In Group 1, 93% of patients reported adverse events, with 64% experiencing general disorders and administration site conditions. Only two patients (14%) reported grade 3 adverse events, involving abdominal and respiratory disorders.

Study Context and Patient Demographics

Cachexia, affecting approximately 80% of PDAC patients, remains a significant challenge associated with poor outcomes. The study population had a median age of 70 years (IQR, 62-75), with male participants comprising 68% and Black patients representing 50% of the cohort.

At baseline, Group 1 patients had a mean weight of 77.9 kg (SD, 19.16) and mean serotonin levels of 165.07 ng/ml (SD, 60.49), while Group 2 started with a mean weight of 90.6 kg (SD, 24.71) and serotonin levels of 296.9 ng/ml (SD, 166.65).

Future Research Direction

The investigators emphasize the need for further research, including ongoing analysis of muscle changes and evaluation of biomarkers in larger patient cohorts. They specifically note the importance of examining the relationship between serotonin levels and pancreatic cancer prognosis.

"A large, randomized study is required to confirm the effect of telotristat [ethyl] in promoting weight stability and ultimately improving overall survival in pancreatic cancer," the researchers concluded.