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

• Published in: The oncologist (Dayton, Ohio) Ohio), 2023-10, Vol.28 (10), p.917-e966
• Main Authors: Tella, Sri Harsha, Foster, Nathan, Qian, Shi, Nguyen, Tran, Borad, Mitesh J, McWilliams, Robert R, Alberts, Steven R, Wee Ma, Wen, Chakrabarti, Sakti, Fruth, Briant, Wessling, Jaclynn, Hartgers, Mindy, Washburn, Leslie, Fernandez-Zapico, Martin E, Hogenson, Tara L, Pitot, Henry, Jin, Zhaohui, Mahipal, Amit
• Format: Article
• Language: English
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biliary Tract - pathology; Carcinoma - drug therapy; Clinical Trial Results; Dosage and administration; Gastrointestinal Neoplasms - drug therapy; Humans; Irinotecan - pharmacology; Irinotecan - therapeutic use; Testing; Trifluridine - pharmacology; Trifluridine - therapeutic use
• ISSN: 1083-7159; 1549-490X; 1549-490X
• DOI: 10.1093/oncolo/oyad144

Abstract Background We sought to determine the safety and efficacy of trifluridine/tipiracil in combination with irinotecan in a phase II trial setting for refractory, advanced unresectable biliary tract carcinoma (BTC). Methods A total of 28 patients (27 were evaluable) with advanced BTCs who progressed on at least one prior systemic therapy were enrolled and were treated with trifluridine/tipiracil 25 mg/m2 (days 1-5 of 14-day cycle) and irinotecan 180 mg/m2 (day 1 of the 14-day cycle). The primary endpoint for the study was 16-week progression-free survival (PFS16) rate. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were pre-specified secondary endpoints. Results Of 27 patients, PFS16 rate was 37% (10/27; 95% CI: 19%-58%), thereby meeting the criteria for success for the primary endpoint. The median PFS and OS of the entire cohort were 3.9 months (95% CI: 2.5-7.4) and 9.1 months (95% CI: 8.0-14.3), respectively. In the patients evaluable for tumor response (n = 20), the ORR and DCR were 10% and 50%, respectively. Twenty patients (74.1%) had at least one grade 3 or worse adverse event (AE), and 4 patients (14.8%) had grade 4 AEs. A total of 37% (n = 10/27) and 51.9% (n = 14/27) experienced dose reductions in trifluridine/tipiracil and irinotecan, respectively. Delay in therapy was noted in 56% of the patients while 1 patient discontinued the therapy, primarily due to hematologic AEs. Conclusion The combination of trifluridine/tipiracil plus irinotecan is a potential treatment option for patients with advanced, refractory BTCs with good functional status and no targetable mutations. A larger randomized trial is needed to confirm these results. (ClinicalTrials.gov Identifier: NCT04072445) This article reports on the safety and efficacy of trifluridine/tipiracil in combination with irinotecan in a phase II trial setting for refractory, advanced unresectable biliary tract carcinoma.