Combining of chemotherapy with targeted therapy for advanced biliary tract cancer: A systematic review and meta-analysis

BACKGROUND: Targeted therapy (TT) has resulted in controversial efficacy as first-line treatment for biliary tract cancer (BTC). More efficacy comparisons are required to clarify the overall effects of chemotherapy (CT) combined with TT and CT alone on advanced BTC. AIM: To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC. METHODS: The PubMed, EMBASE, ClinicalTrials, Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022. Only randomized clinical trials (RCTs) including comparisons between the combination of gemcitabine-based CT with TT and CT alone as first-line treatment for advanced BTC were eligible (PROSPERO-CRD42022313001). The odds ratios (ORs) for the objective response rate (ORR) and hazard ratios (HRs) for both progression-free survival (PFS) and overall survival (OS) were calculated and analyzed. Subgroup analyses based on different targeted agents, CT regimens and tumor locations were prespecified. RESULTS: Nine RCTs with a total of 1361 individuals were included and analyzed. The overall analysis showed a significant improvement in ORR in patients treated with CT + TT compared to those treated with CT alone (OR = 1.43, 95%CI: 1.11-1.86, P = 0.007) but no difference in PFS or OS. Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor (OR = 1.67, 95%CI: 1.17-2.37, P = 0.004) but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor. Notably, patients who received a CT regimen of gemcitabine + oxaliplatin in the CT + TT arm had both a higher ORR (OR = 1.75, 95%CI: 1.20-2.56, P = 0.004) and longer PFS (HR = 0.83, 95%CI: 0.70-0.99, P = 0.03) than those in the CT-only arm. Moreover, patients with cholangiocarcinoma treated with CT + TT had significantly increased ORR and PFS (ORR, OR = 2.06, 95%CI: 1.27-3.35, PFS, HR = 0.79, 95%CI: 0.66-0.94). CONCLUSION: CT + TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes, and highlighting the importance of CT regimens and tumor types in the application of TT.