Efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone in advanced cholangiocarcinoma: A meta-analysis.

Abstract

571 Background: Cholangiocarcinoma (CAA) is increasing. Typically, the majority of patients with CCA are diagnosed at an advanced stage. Immunotherapy (IO) has recently emerged as a transformative cancer treatment by stimulating the patient’s immune system and showing promise across multiple tumor types. However, despite advances with immune checkpoint inhibitors (ICPIs), their effectiveness in biliary tract cancer (BTC) remains limited. In this meta-analysis aims to assess efficacy and safety of adding ICPIs to gemcitabine plus cisplatin (GemCis) versus GemCis alone. Methods: For this meta-analysis, we searched PubMed, Embase, Scopus, Google Scholar for studies published between 2009 and 2025. Eligible studies included randomized clinical trials evaluating ICPIs plus GemCis, and GemCis as first-line treatment for unresectable or metastatic CCA. The primary outcome was OS, and the secondary outcomes included progression-free survival (PFS) and adverse events (AEs) based on Common Terminology Criteria of Adverse Events (CTCAE). For studies presenting Kaplan-Meier curves, individual patient data (IPD) tool was used to reconstruct the data for outcome calculations. Results: A total of 2,000 patients with unresectable or metastatic CCA from clinical trials were included. Median age was 63.7-64 years, with 46-51% male across groups. Of these, 874 received ICPIs plus GemCis, while 1,126 received GemCis. The meta-analysis demonstrated superior efficacy in the ICPIs group, with a median OS of 12.8 months versus 11.0 months (p < 0.001) and a median PFS of 7.0 months versus 5.8 months (p < 0.04). Grade 3/4 adverse events were comparable (72.6% vs 68.7%; p=0.51), with no significant differences in thrombocytopenia, asthenia, vomiting, constipation, diarrhea, nausea, neuropathy, CKD, fever, abdominal events, or cholecystitis. Conclusions: This meta-analysis demonstrates that adding ICPIs to GemCis significantly improves OS and PFS in patients with unresectable or metastatic CCA, while maintaining a comparable safety profile, supporting their use as a first-line treatment option.