Donafenib plus immune checkpoint inhibitors with or without oral fluorouracil chemotherapy drugs (S-1/capecitabine) for patients with resected high-risk biliary tract tumor: A multi-center retrospective study.

Abstract

4236 Background: Chemotherapy combined with Immune Checkpoint Inhibitors (ICIs) and donafenib showed promising efficacy and safety in advanced biliary tract cancer (BTC). Oral fluorouracil chemotherapy drugs S-1 or capecitabine are used as standardized adjuvant therapy for BTC. This study aimed to evaluate the efficacy and safety of donafenib plus ICIs with or without oral fluorouracil chemotherapy drugs as adjuvant therapy in BTC patients with high-risk recurrence factors after radical resection. Methods: This multi-center retrospective study enrolled BTC patients with high-risk recurrence factors who underwent surgical resection at Hunan Provincial People's Hospital, Sichuan Provincial People's Hospital, The First Affiliated of Zhengzhou University, Sir Run Run Shaw Hospital and Jiangsu Provincial People's Hospital from Aug 2022 to Nov 2025. All patients exhibited at least one of the following high-risk recurrence factors: macrovascular invasion, lymph node metastasis, satellite lesion, nerve invasion and the maximum diameter of tumors≥5cm. Patients received adjuvant therapy of donafenib plus ICIs with or without S-1/capecitabine after surgery. The primary endpoint was RFS and secondary endpoints included OS and safety. Results: A total of 50 patients were enrolled, with a median age of 60.5, included 21 Intrahepatic, 18 hilar cholangiocarcinoma and 11 others. Tumor stage I/II/III/IV, 8/10/25/7; R0/R1 resection, 44/6. All patients exhibited a high risk factor of recurrence at least, the rate of macrovascular invasion, lymph node metastasis, satellite lesion, nerve invasion and the maximum diameter of tumors≥5cm are 40.0%, 42.0%, 6.0%, 70.0% and 34.0%. 20 patients received the adjuvant therapy of S-1/ capecitabine plus donafenib with ICIs, and the other 30 patients were treated with donafenib and ICIs. The median follow-up time was 15.2 months (95%CI: 11.17-18.46), 16 patients relapsed. The median RFS was 14.0 months (95% CI: 11.07-NA), and the one-year RFS rate was 63.8%, two-year RFS rate was 45.1%. T staging of tumor is an independent influencing factor on disease recurrence in the multivariate analysis. The RFS in stage T1/2 patients was significantly higher than stage T3/4. The incidence of grade 3 TEAEs stood at 26.0%, including hand-foot syndrome (44%), anaemia (16%), diarrhea (16%) and rash (12%). No patients encountered grade 5 TRAEs. Conclusions: The combination of donafenib plus ICIs with or without oral fluorouracil chemotherapy drugs (S-1/capecitabine) appears to be a promising adjuvant therapy for patients with high-risk biliary tract tumor. Furthermore, no significant safety concerns were observed.