Efficacy and safety of durvalumab plus gemcitabine–cisplatin in combined hepatocellular-cholangiocarcinoma versus cholangiocarcinoma

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer characterized by features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). As cHCC-CCA prognosis often falls between HCC and CCA or resembles CCA, we compared the outcomes of durvalumab plus gemcitabine–cisplatin (GCD) in patients with cHCC-CCA and CCA in a real-world setting. Materials and methods: This retrospective multicenter study included patients with histologically confirmed unresectable or metastatic CCA or cHCC-CCA who underwent first-line GCD at four centers in Taiwan between 2021 and 2025. Outcomes included overall survival (OS), progression-free survival (PFS), tumor response, and safety. Propensity score matching (PSM) was performed to balance baseline characteristics. Results: Among the 175 patients, 154 had CCA and 21 had cHCC-CCA. Before matching, patients with cHCC-CCA more frequently had elevated α-fetoprotein levels and poor biliary drainage; however, these imbalances were resolved after PSM. Before PSM, patients with CCA and cHCC-CCA had median OS of 13.3 months [95% confidence interval (CI) 9.5-17.1] and 13.8 months (95% CI 2.1–25.6, P = 0.60) and median PFS of 5.1 months (95% CI 4.7-5.5) and 5.3 months (95% CI 3.1-7.5, P = 0.40), respectively. After PSM, both OS and PFS rates were similar between the groups. The objective response rate was higher in the cHCC-CCA group (38.1% versus 23.4% before PSM, P = 0.15; 38.1% versus 23.8% after PSM, P = 0.24), whereas the disease control rates were identical (66.7% after PSM). The most common toxicities were hematologic events, with both groups demonstrating similar rates of anemia, thrombocytopenia, leukopenia, and neutropenia. Conclusions: This study demonstrates that patients with cHCC-CCA derive comparable clinical benefit from GCD as those with CCA in terms of efficacy and safety. These findings support the incorporation of immunochemotherapy into the treatment framework for cHCC-CCA and provide a rationale for its use in clinical practice.