Treatment selection for first- and second-line therapy and survival outcomes in advanced biliary tract cancer: A large real-world retrospective analysis.

Abstract

e16197 Background: Biliary tract cancer (BTC) is an aggressive malignancy with constrained therapeutic options. This study aims to observe temporal changes in first-line and second-line treatment strategies for advanced biliary tract cancer (BTC) in real-world settings and evaluate overall survival outcomes across different therapeutic approaches. Methods: This multicentre retrospective study collected clinical and pathological features, treatments, response and survival data from patients with advanced BTC between 2011 and 2024. Kaplan-Meier curves, log-rank tests, propensity score matching and cox regression were used for analysis. Results: Among 1,656 BTC patients, progressive and sustained improvements were observed across first-line treatment modalities: chemotherapy, chemo-immunotherapy, and chemo-immuno-angiogenic therapy (median progression-free survival [mPFS]: 5.5 vs. 6.4 vs. 7.8 months, P < 0.001; median overall survival [mOS]: 11.6 vs. 13.4 vs. 15.3 months, P = 0.001), with particularly pronounced benefits in ICC and GBC patients. Within the chemo-immuno-angiogenic group, gemcitabine plus oxaliplatin (GEMOX)-based regimens outperformed gemcitabine plus cisplatin (GC)-based regimens (mOS: 19.3 vs. 11.3 months, P = 0.005). In second-line treatment (n = 647), immunotherapy-based regimens demonstrated superior efficacy versus chemotherapy-based approaches (mPFS: 4.7 vs. 3.8 months; P = 0.003; mOS: 9.6 vs. 8.1 months; P = 0.027). Among second-line fluorouracil-based chemotherapy regimens, taxane combinations demonstrated numerically superior OS (15.5 months; P = 0.217). Notably, continued immunotherapy after first-line immunotherapy demonstrated significantly better outcomes than switching to non-immunotherapy regimens (mPFS: 4.1 vs. 2.6 months, P = 0.029). Conclusions: Sequential addition of immunotherapy and anti-angiogenic agents to first-line chemotherapy yielded incremental survival benefits, particularly for ICC and GBC, with chemotherapy backbone selection influencing outcomes in combination regimens. In second-line setting, immunotherapy-based regimens outperformed chemotherapy, and maintaining immunotherapy across treatment lines further improved outcomes. These findings provide actionable guidance for optimizing treatment sequencing strategies throughout patients' treatment course.