Cholangiocarcinoma (CCA), a rare and aggressive cancer of the bile ducts, remains a significant therapeutic challenge. Although the TOPAZ-1 trial established the combination of gemcitabine, cisplatin, and durvalumab as the standard of care for first-line treatment, treatment options for patients with disease progression after first-line therapy are limited. The phase 2 Trifluridine/Tipiracil in Combination With Irinotecan as a Second Line Therapy in Patients With Cholangiocarcinoma (TRITICC) trial (NCT04059562) investigated the efficacy and safety of combining trifluridine and tipiracil (FTD/TPI) with irinotecan as a potential second-line treatment for patients with advanced CCA.
The TRITICC trial was a prospective, open-label, single-arm, multicenter study conducted at 6 sites in Germany. Eligible patients had histologically confirmed locally advanced or metastatic biliary tract cancer and had experienced disease progression following first-line gemcitabine-based therapy. Participants received FTD/TPI 25 mg/m² orally twice daily on days 1 to 5 of each 14-day cycle combined with irinotecan 180 mg/m² intravenously on day 1 of each cycle. The primary endpoint of the study was progression-free survival (PFS), whereas secondary endpoints included the PFS rate at 4 months, overall survival (OS), objective response rate, and quality of life.
A total of 28 patients were enrolled in the study. The median PFS was 3.1 months, with PFS rates of 35% (95% confidence interval [CI], 21%-58%) at 4 months, 30% (95% CI, 17%-54%) at 6 months, and 13% (95% CI, 4.7%-37%) at 12 months. The median OS was 10 months, with OS rates of 74% at 6 months and 38% at 12 months. Notably, patients with intrahepatic CCA appeared to derive a benefit from the treatment. Among 27 evaluable patients, partial responses were observed in 11.1% of patients, whereas 40.7% achieved stable disease. Disease progression occurred in 48.1% of patients.
The combination therapy demonstrated a manageable safety profile, with the most common adverse events including neutropenia, thrombocytopenia, gastrointestinal symptoms, and fatigue. No severe, unmanageable, or unexpected toxicities were observed. However, quality of life, as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, declined moderately, with the mean Global Health Status score dropping from 56.2 at baseline to 46.4 at the end of treatment.
The combination of FTD/TPI with irinotecan showed promising efficacy with a manageable safety profile in patients with CCA after gemcitabine-based therapy. These findings provide a foundation for further exploration of irinotecan-based regimens to address the unmet needs of this challenging patient population. The planned follow-up TRITICC-2 study will evaluate the efficacy of pegylated irinotecan in combination with FTD/TPI, which could offer improved outcomes over conventional irinotecan.
Kehmann L, Gonzalez-Carmona MA, Berres M, et al. First results of an open-label, single arm phase II trial investigating the efficacy and safety of trifluridine/tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Poster 411.
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