Real-world outcomes of fluorouracil-based second-line therapy in patients with advanced biliary tract cancer refractory to gemcitabine and cisplatin-based treatment.

Background: The prognosis for patients with advanced biliary tract cancer (BTC) who have not responded to gemcitabine and cisplatin (GP)-based therapy is dismal. Fluorouracil (5-FU)-based chemotherapy could be considered for those patients who are refractory to GP-based treatments. Our study aimed to evaluate the real-world efficacy and safety of 5-FU-based chemotherapy for BTC patients who had progressed after gemcitabine-based treatment. Methods: This study analyzed patients from Seoul St. Mary's Hospital and St. Vincent's Hospital with advanced BTC who had previously failed treatment with GP-based chemotherapy. From June 2020 and May 2024, these patients received 5-FU-based chemotherapy as a second-line treatment. The 5-FU-based systemic treatments encompassed 5-FU, leucovorin, and oxaliplatin (FOLFOX); 5-FU, leucovorin, and liposomal irinotecan (Nal-IRI/FL); and 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Our investigation focused on evaluating the survival outcomes and safety profiles of each regimen within this cohort. Results: In our analysis of 147 patients, the primary tumor sites were distributed with 56 (38.1%) having intrahepatic cholangiocarcinoma, 51 (34.7%) with extrahepatic cholangiocarcinoma, and 40 (27.2%) with gallbladder cancer. Regarding the 5-FU-based regimens, 57 patients (38.8%) were treated with FOLFOX, 56 (38.1%) with Nal-IRI/FL, and 34 (23.1%) with FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% confidence interval (CI), 2.0-2.6) and 4.8 months (95% CI, 3.8-5.8), respectively. Poor performance status and higher histologic grade were associated with worse PFS and OS, while female gender and prior surgery were linked to improved OS. FOLFOX and Nal-IRI/FL demonstrated comparable efficacy, with a median OS of 5.4 months (95% CI, 3.5-7.3) for FOLFOX and 4.7 months (95% CI, 2.6-6.9) for Nal-IRI/FL, and no significant differences were observed across subgroups. Grade 3 or higher neutropenia and biliary events were less frequent with FOLFOX, which also showed a lower incidence of adverse events and higher relative dose intensity than Nal-IRI/FL or FOLFIRINOX. Conclusion: In patients with advanced BTC who failed GP treatment, the FOLFOX regimen demonstrated comparable efficacy, and a more favorable safety profile compared to other 5-FU-based treatments. Given its favorable toxicity profile in a real-world setting, FOLFOX should be considered a standard second-line treatment option.