Analysis of the effectiveness and safety of lenvatinib/bevacizumab combined with PD-1/PD-L1 inhibitors and GEMOX in the first-line treatment of advanced biliary tract carcinoma

To assess the efficacy and safety of lenvatinib/bevacizumab combined with programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors and gemcitabine/oxaliplatin (GEMOX) as first-line treatments in patients with advanced biliary tract cancer (BTC). Patients with advanced BTC who received lenvatinib/bevacizumab combined with PD-1/PD-L1 inhibitors plus gemcitabine/oxaliplatin (GEMOX) chemotherapy were retrospectively screened. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors for survival were analyzed. A total of 172 individuals were enrolled and categorized into four groups: Group A received GEMOX plus PD-1 antibody (sintilimab or camrelizumab) and lenvatinib; group B received GEMOX and PD-1 antibody (sintilimab or camrelizumab) and bevacizumab; group C received GEMOX and PD-1 antibody (sintilimab or camrelizumab); and group D received GEMOX alone. The median OS was 13.63 months (95% confidence interval [CI]: 12.37-14.89), 12.41 months (95% CI: 10.67-12.32), 11.23 months (95% CI: 9.39-13.07), and 8.86 months (95% CI: 7.28-10.44) in groups A, B, C, and D, respectively (P = 0.312). In groups A, B, C, and D, the median PFS was 12.42 months, 11.05 months, 8.89 months, and 6.02 months. A statistically significant difference was observed (t = 2, 95% CI: 11.31-13.53, P < 0.01). The ORR was 45.00% (17/40) in group A, 34.78% (16/46) in group B, 16.67% (5/30) in group C, and 17.86% (10/56) in group D. The DCR was 87.50% (35/40), 78.26% (36/46), 76.67% (23/30), and 58.93% (33/56) in groups A, B, C, and D, respectively. In addition, regression analysis showed that patients' metastasis site, whether the neutrophil-lymphocyte ratio was < 2.3, and whether chemotherapy was administered through hepatic artery embolization and was independent prognostic factors influencing median OS and PFS. Almost all patients included in the study experienced treatment-related adverse events (TRAEs) of varying degrees of severity, with grade 1-2 adverse events predominating. Lenvatinib/bevacizumab combined with programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors and gemcitabine/oxaliplatin (GEMOX) represent an effective and tolerable regimen for advanced BTC in a multicenter retrospective real-world study.