Nab-paclitaxel-based chemotherapy with or without anti-PD-(L)1 immunotherapy as a second-line treatment for advanced biliary tract cancer: a real-world retrospective study

Background: Second-line options for biliary tract cancer (BTC) are limited. While nab-paclitaxel has demonstrated certain antitumor activity, evidence remains scarce. With gemcitabine–cisplatin plus anti-programmed death-ligand 1 (PD-(L)1) established as the first-line standard, the benefit of second-line immunotherapy—especially in patients without prior anti-PD-(L)1 exposure—remains unclear. Objectives: To evaluate the efficacy and safety of nab-paclitaxel-based second-line treatments for advanced BTC, and compare outcomes between regimens with and without anti-PD-(L)1. Design: This is a real-world retrospective study. Methods: This study reviewed BTC patients who received second-line nab-paclitaxel-based therapy at West China Hospital between August 2018 and August 2023. The primary endpoint was overall survival (OS) in the entire population. Secondary endpoints were progression-free survival (PFS), response rate, adverse events (AEs) in the entire population, and comparison of survival outcomes and response rate between the chemo-anti-PD-(L)1 and chemotherapy groups. Results: Among 84 patients (41 in the chemo-anti-PD-(L)1 group and 43 in the chemotherapy group), the median OS was 15.17 months (95% confidence interval (CI), 12.63–21.43), median PFS was 5.40 months (95% CI, 3.23–8.03), objective response rate (ORR) was 21.43% (95% CI, 13.22–31.74), and disease control rate (DCR) was 60.71% (95% CI, 49.45–71.20). Common grade 3–4 AEs were leukopenia (21.4%), neutropenia (17.9%), and anemia (13.1%). Hepatitis (14.6%) was the most frequent immune-related AE. Although a numerical trend favored the chemo-anti-PD-(L)1 group, no statistically significant differences were observed in OS (16.9 vs 14.6 months), PFS (7.3 vs 4.6 months), ORR (29.3% vs 13.9%), or DCR (68.3% vs 53.5%). In the entire cohort, radical surgery improved OS. In addition, patients with a baseline neutrophil-to-lymphocyte ratio ⩾3 and a ⩽30% reduction in carbohydrate antigen 19-9 from an initially elevated level during treatment had worse OS and PFS. Conclusion: Nab-paclitaxel-based regimens represent a promising second-line treatment option for BTC. Although the improvement was not statistically significant, adding anti-PD-(L)1 therapy showed a trend toward improved survival. Trial registration: ChiCTR2500096599.