Efficacy of Durvalumab‐Tremelimumab Treatment in Combination With Locoregional Therapy in Unresectable Hepatocellular Carcinoma: A Preliminary Study

Systemic therapy with immune checkpoint inhibitors for advanced hepatocellular carcinoma (HCC) treatment has demonstrated high response rates. Durvalumab plus tremelimumab (Dur/Tre) has been approved for HCC treatment and has become a first-line systemic therapy along with atezolizumab plus bevacizumab. However, there is early withdrawal owing to immune-related adverse effects, while others required sequential therapy owing to the lack of early therapeutic effects. Herein, we investigated the clinical characteristics of patients with progressive disease (PD) who were treated with Dur/Tre in addition to locoregional therapy. We retrospectively evaluated eight patients with HCC, who were treated with Dur/Tre in March 2025 and continued Dur/Tre until PD was treated with locoregional therapy. Additionally, immunological changes, and treatment efficacy during continuation therapy were also assessed. Treatment efficacy was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). At Dur/Tre induction, patients (mean age, 76.88 years, all male) had alcoholic liver disease (n=3), nonalcoholic steatohepatitis (n=4), or hepatitis B virus (n=1). Six patients received Dur/Tre as first-line therapy, two were treated with atezolizumab plus bevacizumab as pretreatment, and the mean number of Dur/Tre cycles was 5.2. Neutrophil to lymphocyte ratio (NLR) was 2.14±1.51 at the time of Dur/Tre induction and worsened to 2.80±1.91 at the time of PD but significantly improved to 2.08±1.14 after locoregional therapy (p=0.047). Des-gamma-carboxy prothrombin (DCP) levels also decreased significantly after locoregional therapy (p=0.021). One patient responded partially, and seven achieved disease stability with continued treatment. Continued Dur/Tre therapy may be effective in patients with improved NLR and DCP levels after adjunct locoregional therapy. Further studies involving larger patient cohort might determine strategic addition of locoregional therapy in PD.