Phase II Trial of Trifluridine/Tipiracil in Patients with Advanced, Refractory Biliary Tract Carcinoma

• Published in: The oncologist (Dayton, Ohio) Vol. 25; no. 5; pp. 380 - e763
• Main Authors: Chakrabarti, Sakti, Zemla, Tyler J., Ahn, Daniel H., Ou, Fang‐Shu, Fruth, Briant, Borad, Mitesh J., Hartgers, Mindy L., Wessling, Jaclynn, Walkes, Rachel L., Alberts, Steven R., McWilliams, Robert R., Liu, Minetta C., Durgin, Lori M., Bekaii‐Saab, Tanios S., Mahipal, Amit
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-05-2020
• Subjects: Clinical Trial Results
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2019-0874

Lessons Learned
Trifluridine/tipiracil (FTD/TPI) shows promising antitumor activity in heavily pretreated patients with advanced biliary tract carcinoma, including patients with 5‐fluorouracil refractory tumors.
FTD/TPI has an acceptable safety profile and should be studied further in patients with advanced biliary tract carcinoma after progression on standard first‐line therapy.
Background
Patients with advanced biliary tract carcinoma (BTC) refractory to first‐line therapy lack an established second‐line option. Trifluridine/tipiracil (FTD/TPI) has activity in both fluoropyrimidine‐sensitive and ‐resistant tumors, which led us to conduct a single arm phase II trial to evaluate the safety and efficacy of FTD/TPI for patients previously treated for advanced BTC.
Methods
Patients with advanced BTC previously treated with at least one line of chemotherapy were enrolled and treated with FTD/TPI until disease progression or unacceptable toxicity. The primary endpoint target was to have at least 6 patients who were progression free and alive at 16 weeks among 25 evaluable patients. Secondary endpoints included overall survival (OS), overall response rate (ORR), progression‐free survival (PFS), and toxicity.
Results
Of 27 evaluable patients, 59.3% received at least three prior lines of therapy, and 81.5% had previous exposure to fluoropyrimidine. Eight (32%, 95% confidence interval [CI], 14.9%–53.5%) patients were progression free at 16 weeks in the primary analysis population (n = 25), which met the predefined efficacy criteria. Median PFS and OS were 3.8 (95% CI, 2–5.8 months) and 6.1 (95% CI, 4.4–11.4 months) months, respectively. No objective responses were seen. There were no unexpected safety signals noted.
Conclusion
FTD/TPI demonstrated promising antitumor activity, with acceptable toxicity, in heavily pretreated patients with advanced BTC.