Abstract 328P
Background
Patients with refractory pancreatic cancer have limited therapeutic option and dismal prognoses. Trifluridine/tipiraci (FTD/TPI) has demonstrated activity in pancreatic cancer and fluoropyrimidine-resistant tumors in pre-clinical studies. However, no clinical data exists to date. We aimed to evaluate the efficacy and safety of TAS-102 in patients with fluoropyrimidine refractory pancreatic cancer.
Methods
This is a single-arm phase II trial. Patients of advanced, metastatic pancreatic cancer with ECOG PS 0-1 and adequate organ function, who had progressed after one or more line(s) of chemotherapy were enrolled. Patients were treated with TAS-102 at a dose of 35mg/m2 twice daily on days 1-5 and 8-12 of a 28-day cycle until disease progression or unacceptable toxicity. The primary endpoint was 16-week progression-free survival (PFS) rate. Secondary endpoints included median PFS, median overall survival (OS), disease control rate (DCR), and toxicities. This trial is registered with ClinicalTrials.gov (NCT04923529).
Results
Between March 2021, and June 2023, a total of 28 patients were enrolled. The median age was 64 years (range: 49-80) and 16 (57.1%) were male. All 28 patients (100%) received prior chemotherapy regimens containing fluoropyrimidine. 23 patients (82.1%) received 2 or more lines of chemotherapy. After a median follow-up of 4.8 months, the 16-week PFS rate was 53.6% (15/28; 95% confidence interval [CI], 37.4-69.8%). The median PFS was 3.7 months (95% CI, 2.1-5.3 months) and the median OS was 4.5 months (95% CI, 3.6-5.4 months). The median number of treatment cycles was 2 (range: 1-12). The DCR was 50% (14/28; 95% CI, 30.7-69.4%). The most common grade 3 or worse adverse events were neutropenia (n=9, 32.1%), anemia (n=4, 14.3%), and increase in bilirubin level (n=4, 14.3%) without new safety signals. Neutrophil to lymphocyte ratio (NLR) > 5 was associated with the worse PFS (hazard ratio HR: 7.6; 95% CI, 2.5-23.4) and OS (HR: 7.4; 95% CI, 2.5-21.4).
Conclusions
This is the first prospective study to demonstrate the promising efficacy and acceptable safety of TAS-102 in patients with pancreatic cancer refractory to fluoropyrimidine. Further randomized trial is warranted.
Clinical trial identification
NCT04923529.
Legal entity responsible for the study
Dr. Chiang Chi Leung.
Funding
Taiho Pharmaceutical Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.