Safety and efficacy of PD-1/PD-L1 inhibitors combined with albumin-bound paclitaxel and fluorouracil-based agents as second-line therapy in biliary tract cancers.

backgroundBiliary tract cancers (BTCs) are a group of highly aggressive malignancies with limited therapeutic options. Gemcitabine plus cisplatin (GemCis) remains the standard first-line regimen; however, the efficacy of currently recommended second-line therapies remains unsatisfactory. Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 or its ligand (PD-1/PD-L1) have demonstrated antitumor activity in a subset of patients with BTC, while albumin-bound paclitaxel (nab-paclitaxel) has shown efficacy across multiple solid tumors. This study aimed to evaluate the real-world safety and efficacy of a second-line combination regimen comprising PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) in patients with advanced BTCs.

methodsThis retrospective study included patients with advanced BTCs who received second-line therapy with a combination of PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) at the Second Affiliated Hospital of Nanchang University between January 2019 and May 2025. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and treatment-related adverse events (TRAEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and TRAEs.

resultsA total of 36 patients were enrolled, including 17 (47.2%) with gallbladder cancer, 17 (47.2%) with intrahepatic cholangiocarcinoma, and 2 (5.6%) with extrahepatic cholangiocarcinoma. According to RECIST version 1.1, no complete responses (CR) were observed; four patients (11.1%) achieved a partial response (PR), 19 (52.8%) had stable disease (SD), and 13 (36.1%) experienced progressive disease (PD), yielding an ORR of 11.1% and a disease control rate (DCR) of 63.9%. The median progression-free survival (PFS) was 6.8 months (95% confidence interval [CI]: 4.2-10.2), and the median overall survival (OS) was 10.8 months (95% CI: 7.2-16.2). No significant differences in PFS (6.8 vs. 7.9 months, P = 0.55) or OS (11.1 vs. 10.8 months, P = 0.68) were observed between patients who had received prior immunotherapy and those who had not. The most common grade 3-4 TRAEs were chemotherapy-related myelosuppression, decreased appetite, and elevated total bilirubin. One patient developed hand-foot syndrome, and another experienced immune-mediated pneumonitis. No treatment-related deaths were reported.

conclusionThe combination of PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) demonstrated manageable toxicity and modest clinical activity as a second-line therapy for advanced BTCs. This regimen may represent a feasible treatment option for patients who progress following first-line therapy. Moreover, continued administration of this immunotherapy-based combination beyond initial progression may confer survival benefits in select patients.