Background and Aims: Durvalumab plus tremelimumab (Dur/Tre) therapy is expected to have good therapeutic efficacy for patients with unresectable hepatocellular carcinoma (u‐HCC). We previously reported that the neutrophil‐to‐lymphocyte ratio (NLR) during atezolizumab plus bevacizumab therapy in u‐HCC patients was a useful marker for predicting the therapeutic response. Therefore, we investigated whether the NLR during Dur/Tre therapy could predict treatment outcomes in patients with u‐HCC.Design: The present study included 64 u‐HCC patients treated with Dur/Tre and evaluated for their initial response by dynamic computed tomography or magnetic resonance imaging at least once until December 2024. Alpha‐fetoprotein (AFP) and des‐gamma‐carboxyprothrombin (DCP) ratios were defined as follows: the pretreatment levels of AFP and DCP were set to 1, and the AFP and DCP ratios to pretreatment were calculated at the start of the second course of Dur/Tre therapy.Results: Of the 64 HCC patients, 34 patients (53%) achieved a disease control rate (non‐PD) at the initial evaluation. The NLR at the start of the second course (NLR‐2c) tended to be lower in patients with non‐PD than progressive disease (p = 0.133), and the optimal cutoff value was 5.75. Patients with NLR‐2c ≥ 5.75 had a shorter progression‐free survival (PFS) than those with NLR‐2c < 5.75 (median: 1.7 vs. 5.5 months, p = 0.002). Multivariate analysis showed that NLR‐2c ≥ 5.75 (HR 4.66; p < 0.001) and AFP ratio ≥ 0.933 (HR 4.32; p = 0.004) were significantly associated with poor PFS.Conclusions: The NLR‐2c value is useful for predicting PFS in u‐HCC patients treated with Dur/Tre therapy.

Background & Aims: Relationships of serum C‐C motif chemokine ligand 5 (CCL5) and C‐X‐C motif chemokine ligand 10 (CXCL10) levels with hot immune features have been reported in patients with hepatocellular carcinoma (HCC). Therefore, we examined the utility of their levels for predicting the efficacy of atezolizumab plus bevacizumab (Atez/Bev) in patients with HCC.Design: In total, 98 patients with HCC treated with Atez/Bev were enrolled, and their initial responses were evaluated at least once via dynamic computed tomography or magnetic resonance imaging. Serum CCL5 and CXCL10 levels were assessed by enzyme‐linked immunosorbent assay before treatment and at the start of the second course of Atez/Bev therapy, and their relationships with treatment efficacy were determined.Results: No analyzed factor was associated with the initial therapeutic response. Among the 56 patients with Barcelona Clinic Liver Cancer (BCLC) stage C, serum CXCL10 levels at the beginning of course two (CXCL10‐2c) tended to be higher in responders than in non‐responders in the initial evaluation, and its optimal cutoff level of 690 pg/mL could be used to stratify patients regarding overall survival (OS; high vs. low: not reached vs. 17.6 months, p = 0.034) and progression‐free survival (high vs. low: 13.6 vs. 5.1 months, p = 0.014). In multivariate analysis, high CXCL10 levels and neutrophil‐to‐lymphocyte ratios at the start of course two and Child–Pugh stage A at baseline were independent predictive factors of improved OS.Conclusions: Serum CXCL10‐2c levels were predictive of Atez/Bev efficacy in patients with BCLC stage C HCC.

We retrospectively evaluated the impact of therapeutic modifications of atezolizumab (Atezo) plus bevacizumab (Bev) therapy (Atezo/Bev), including the interruption or discontinuation of both Atezo and Bev, and the reduction or discontinuation of Bev, on the outcome of patients with unresectable hepatocellular carcinoma (uHCC) (median observation period: 9.40 months). One hundred uHCC from five hospitals were included. Therapeutic modifications without discontinuation of both Atezo and Bev (n = 46) were associated with favorable overall survival (median not reached; hazard ratio (HR): 0.23) and time to progression (median: 10.00 months; HR: 0.23) with no therapeutic modification defined as the reference. In contrast, the discontinuation of both Atezo and Bev without other therapeutic modifications (n = 20) was associated with unfavorable overall survival (median: 9.63 months; HR: 2.72) and time to progression (median: 2.53 months; HR: 2.78). Patients with modified albumin–bilirubin grade 2b liver function (n = 43) or immune-related adverse events (irAEs) (n = 31) discontinued both Atezo and Bev without other therapeutic modifications more frequently (30.2% and 35.5%, respectively) than those with modified albumin–bilirubin grade 1 (10.2%) and without irAEs (13.0%). Patients with objective response (n = 48) experienced irAEs more frequently (n = 21) than those without (n = 10) (p = 0.027). Avoiding the discontinuation of both Atezo and Bev without other therapeutic modifications may be the optimal management of uHCC.