The efficacy of second‐line chemotherapy for advanced biliary tract cancer: A systematic review and network meta‐analysis

Abstract Background This network meta‐analysis (NMA) aims to provide evidence‐based guidance for selecting the second‐line chemotherapy for biliary tract cancer (BTC). Methods A comprehensive literature search was conducted on PubMed, Cochrane, and EMBASE through July 2024. Inclusion criteria involved: (1) patients underwent second‐line chemotherapy following platinum‐based first‐line therapy, (2) intervention/comparator groups consisted of various chemotherapeutic agents, and (3) outcomes measured as hazard ratio (HR) of overall survival (OS) and progression‐free survival (PFS) in randomized controlled trials (RCTs) and cohort studies. Results Outcomes were measured as HR of OS and PFS in RCTs and cohort studies. The eight studies consisting of 1621 patients were selected. In the NMA for OS, 5FU_plus_Plat (fluorouracil plus oxaliplatin or cisplatin; HR 0.52, 95% confidence interval [CI]: 0.30–0.91), nal‐IRI_5FU_LV (nano‐liposomal irinotecan plus fluorouracil and LV; HR 0.54 [95% CI: 0.32–0.92]), and FOLFOX (fluorouracil plus oxaliplatin; HR 0.69 [95% CI: 0.50–0.96]) demonstrated significant benefits in OS when compared to control. For PFS, nal‐IRI_5FU_LV (HR 0.61 [95% CI: 0.44–0.85]) provided a significant advantage over 5FU. Conclusions Second‐line chemotherapy for BTC after the failure of gemcitabine plus platinum as first‐line therapy, nal‐IRI_5FU_LV appears to be the most promising second‐line therapy in terms of both OS and PFS.