Surufatinib plus anti‐PD‐1/PD‐L1 antibody as second‐line therapy for advanced biliary tract cancer: A single‐centre investigator‐initiated trial

Abstract Objective To explore the efficacy and safety of surufatinib in combination with anti‐PD‐1/PD‐L1 antibodies (with or without chemotherapy) in patients with advanced BTC after failure of first‐line treatment. Methods 24 patients with advanced BTC who failed first‐line treatment were admitted to our centre from March 2023 to August 2024 and treated with surufatinib combined with anti‐PD‐1/PD‐L1 antibodies (with or without chemotherapy). The primary endpoint was PFS, and the secondary endpoints were ORR, DCR, OS and safety indicators. Results There were 10 cases of intrahepatic cholangiocarcinoma, 5 cases of hilar cholangiocarcinoma, 2 cases of extrahepatic cholangiocarcinoma, and 7 cases of gallbladder cancer. There were 16 cases of combined chemotherapy and immunotherapy, and 8 cases of combined immunotherapy alone. The median PFS of all patients was 3.81 months (95%CI 2.46–4.50), the median OS was 10.48 months (95%CI 6.54–16.43), and the ORR was 20.8% (95%CI 7.1%–42.2%). The DCR was 54.2% (95%CI 32.8%–74.4%). Subgroup analysis showed that the median PFS of cholangiocarcinoma group was 3.81months (95%CI 2.07–4.50), while the median OS was 9.56months (95%CI 6.34–16.43). The median PFS of gallbladder cancer was 3.81 months (95%CI 2.07–4.50), while the OS was 11.11 months (95%CI 3.42–11.11). The median PFS in the combined chemotherapy plus immunization group was 3.91months (95%CI 2.46–5.16), and the median OS was 8.80 months (95%CI 6.34–16.34). The median PFS in the combined immunotherapy alone group was 3.22 months (95%CI 1.08–4.70), and the median OS was 10.48 months (95%CI 2.53–11.2). TRAE occurred in 15 cases (62.5%) which mainly including hypothyroidism, transaminase elevation and fatigue. While the incidence of grade 3 and above AE was 12.5% (3/24), mainly including leukopenia and thrombocytopenia. Conclusion Surufatinib combined with anti PD‐1/PD‐L1 antibodies was effective and tolerable in second‐line treatment of advanced BTC. It is worthy of further in‐depth exploration through multi‐centre and large‐sample clinical trials.