Abstract
Background/Objectives: Several chemotherapeutic regimens and targeted therapies are currently established as standard second-line treatments for patients with advanced biliary tract cancer (BTC). However, evidence regarding the benefits of treatment after first-line therapy failure remains limited, particularly among Thai populations. This study aimed to explore the efficacy of second-line chemotherapy in patients with advanced BTC. Methods: We conducted a single-institution, retrospective study including patients with locally advanced or metastatic BTC who experienced disease progression following first-line treatment between January 2017 and December 2019. Overall survival (OS) was defined as the primary endpoint. The secondary endpoint was the restricted mean survival time (RMST). To minimize confounding, propensity scores were estimated and applied using inverse probability of treatment weighting (IPTW). Results: A total of 110 patients were included, of whom 69 (62%) received second-line chemotherapy in combination with best supportive care (2LCMT + BSC), while 41 (38%) received best supportive care (BSC) alone. The majority of cases were intrahepatic cholangiocarcinoma (73.9% and 70.7% in each group, respectively). The median OS was 5.3 months (95% CI 3.5-7.0) in the 2LCMT + BSC group and 1.0 months (95% CI 0.5-1.9) in the BSC-only group (unadjusted HR 0.40, 95% CI 0.26-0.59; p < 0.001). In IPTW-adjusted flexible parametric regression analysis, second-line chemotherapy was associated with a 53% reduction in the risk of death compared with BSC alone (p = 0.009). The restricted mean survival time (RMST) differences between groups at 3, 6, and 12 months were 1.3 months (95% CI 0.9-1.6; p < 0.001), 2.6 months (95% CI 1.9-3.3; p < 0.001), and 3.9 months (95% CI 2.7-5.1; p < 0.001), sequentially. Conclusions: These findings demonstrate that second-line chemotherapy provides a significant overall survival benefit compared with best supportive care alone in patients with advanced BTC.