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This meta-analysis evaluates the effectiveness and safety of immunotherapy combined with gemcitabine and cisplatin in advanced cholangiocarcinoma.

May 29, 2026

Durvalumab or pembrolizumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy for advanced cholangiocarcinoma: A meta-analysis.

Key Points

This meta-analysis evaluates the effectiveness and safety of immunotherapy combined with gemcitabine and cisplatin in advanced cholangiocarcinoma.
Systematic review of randomized controlled trials and cohort studies from 2009 to 2025.
Primary endpoint was overall survival; secondary endpoints included progression-free survival and adverse events.
Data from the trials were pooled using random-effects models, and heterogeneity was assessed.
GemCis plus durvalumab showed the highest median overall survival of 14.1 months compared to 12.8 months for pembrolizumab and 9.27 months for GemCis alone.
In RCTs, IO plus GemCis improved overall survival significantly (HR 0.78, 95% CI 0.71–0.86, p<0.001) without a significant difference in progression-free survival.
Grade 3-4 adverse events were rare, with thrombocytopenia more common in the pembrolizumab group.

Abstract

4160 Background: Cholangiocarcinoma (CCA) is a rare, aggressive malignancy of the bile duct epithelium with rising incidence and mortality. Curative surgery is feasible in few cases; for unresectable or metastatic disease, systemic therapy is standard. Gemcitabine plus cisplatin (GemCis) has been the first-line backbone, but phase 3 trials (TOPAZ-1 and KEYNOTE-966) demonstrated overall survival (OS) benefit with added immune checkpoint inhibitors (durvalumab or pembrolizumab). This systematic review and meta-analysis evaluates the efficacy and safety of immunotherapy (IO) plus GemCis versus GemCis alone in advanced CCA. Methods: We systematically searched PubMed, Embase, Scopus, and Google Scholar for English-language studies (2009–2025) including randomized controlled trials (RCTs) and cohort studies of first-line GemCis alone or with durvalumab or pembrolizumab in unresectable/metastatic CCA. Primary endpoint: OS. Secondary: progression-free survival (PFS) and grade 3-4 adverse events (AEs) per CTCAE. Kaplan-Meier curves were digitized, and individual patient data reconstructed using IPD tools for pooled estimates. Random-effects models generated hazard ratios (HRs) and pooled medians; heterogeneity assessed via I². Results: We included 3,703 patients from TOPAZ-1, KEYNOTE-966, ABC-01/02, and six cohort studies: 1,737 on GemCis alone, 1,433 on GemCis + durvalumab, and 533 on GemCis + pembrolizumab. In the full meta-analysis, GemCis + durvalumab showed the best outcomes (median OS 14.1 months, PFS 7.38 months) versus GemCis + pembrolizumab (OS 12.8 months, PFS 6.62 months) and GemCis alone (OS 9.27 months, PFS 5.81 months). Restricting to RCTs only, IO + GemCis improved OS versus GemCis alone (median 12.82 vs. 11.1 months; HR 0.78, 95% CI 0.71–0.86, p<0.001), with no significant PFS difference (p=0.20). Grade 3-4 AEs were infrequent across arms; thrombocytopenia was higher with pembrolizumab (p=0.0002), but other severe toxicities were comparable. Conclusions: Adding immunotherapy to GemCis significantly enhances survival in unresectable/metastatic CCA, with durvalumab + GemCis providing the most pronounced benefit in this pooled analysis incorporating RCTs and real-world cohorts. Regimens were well-tolerated with manageable toxicity. These findings reinforce chemoimmunotherapy as first-line standard and highlight potential differential efficacy between PD-L1 and PD-1 inhibitors warranting further study.

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Durvalumab or pembrolizumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy for advanced cholangiocarcinoma: A meta-analysis.

Key Points

Abstract

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