PD-1/PD-L1 inhibitors combined with chemotherapy as first-line treatment for advanced biliary tract cancer: a...

To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy as first-line treatment for advanced biliary tract cancer (BTC).

PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were searched for RCTs and retrospective studies. Meta-analysis was performed using R 4.6.1 software with the meta (v8.5-0) and metafor (v5.0-1) packages. The full R code and datasets are provided in the supplementary material to ensure reproducibility.

Part I included 5 RCTs with 2,000 patients; of these, only 2 phase III RCTs (TOPAZ-1 and KEYNOTE-966, n = 1,754) reported OS and PFS data, while all 5 RCTs reported ORR and DCR data; Part II included 6 retrospective studies with 1,253 patients. RCT meta-analysis showed: OS was significantly improved (HR = 0.80, 95% CI: 0.72-0.89, p < 0.001); PFS was also significantly improved (HR = 0.81, 95% CI: 0.71-0.93, p = 0.002); ORR was significantly higher (RR = 1.38, 95% CI: 1.02-1.87, p = 0.037). Retrospective study meta-analysis showed: PFS was significantly superior (HR = 0.52, 95% CI: 0.43-0.63, p < 0.001); OS was significantly prolonged (HR = 0.61, 95% CI: 0.42-0.87, p = 0.017); ORR (RR = 1.97, 95% CI: 1.43-2.71, p = 0.004) and DCR (RR = 1.26, 95% CI: 1.09-1.45, p = 0.014) were also significantly higher. Neither part showed significantly increased severe adverse events.

PD-1/PD-L1 inhibitors plus chemotherapy significantly improves survival outcomes and objective response rate in advanced BTC without increasing severe adverse event risk.

PROSPERO. Unique Identifier: CRD420261401842 URL: https://www.crd.york.ac.uk/prospero/display_record.php?