Biomarker, efficacy and safety analysis of transcatheter arterial chemoembolization combined with atezolizumab and bevacizumab for unresectable hepatocellular carcinoma.

Objective: Transcatheter arterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (Atezo-Bev) [Atezo-Bev-TACE] has shown promising therapeutic efficacy in patients with unresectable hepatocellular carcinoma (uHCC). However, there is currently no published research on biomarkers that can predict the treatment outcomes of Atezo-Bev-TACE. This study aims to evaluate the predictive value of the baseline neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in uHCC patients undergoing Atezo-Bev-TACE treatment.

Methods: This retrospective study included uHCC patients who received Atezo-Bev-TACE and tyrosine kinase inhibitors (TKIs) at the First Affiliated Hospital of the University of Science and Technology of China between November 1, 2020, and November 1, 2023. The primary endpoint of the study was the correlation between baseline NLR and PLR with overall survival (OS) and progression-free survival (PFS). The secondary endpoints were the efficacy and safety of the Atezo-Bev-TACE regimen.

Results: Among the 71 enrolled patients with uHCC who received Atezo-Bev-TACE therapy, the objective response rate was 55.0%, with a median OS of 20.0 months (95% confidence interval [CI] 17.4-21.0 months) and a median PFS of 10.4 months (95% CI 7.7-13.1 months). Patients with tumor response had significantly lower baseline NLR and PLR values compared to those without response (2.5 vs. 4.0, P < 0.001; 106.9 vs. 131.3, P = 0.001). The optimal cut-off values for NLR and PLR were determined to be 2.9 and 148.0, respectively, based on receiver operating characteristic curves. Patients with baseline NLR < 2.9 had significantly longer median OS (not reached vs. 17.8 months, P = 0.014) and improved median PFS (15.6 months vs. 9.3 months, P = 0.034) compared to those with NLR ≥ 2.9. Similarly, patients with baseline PLR < 148.0 had a significantly better median OS (20.0 months vs. 12.0 months, P = 0.004) and longer median PFS (13.7 months vs. 6.4 months, P < 0.001) compared to those with PLR ≥ 148.0. Univariate and multivariate Cox regression analyses identified baseline PLR ≥ 148.0 as an independent risk factor for poorer survival outcomes. Additionally, most adverse events (AEs) observed during Atezo-Bev-TACE treatment were grade 1-2, with fewer grade 3-4 AEs, and no grade 5 AEs were reported. Comparative analysis between the Atezo-Bev-TACE group (71 patients) and the TKIs-TACE group (63 patients) demonstrated that the ORR of the TKIs-TACE group was 34.9%, lower than that of the Atezo-Bev-TACE group (55.0%). No statistically significant differences were observed in baseline characteristics between the two groups before treatment. The median OS in the Atezo-Bev-TACE group was 20.0 months, significantly superior to the 14.7 months in the TKIs-TACE group (P = 0.005). Similarly, the median PFS in the Atezo-Bev-TACE group was 10.4 months, significantly better than the 7.8 months in the TKIs-TACE group (P = 0.008).

Conclusion: A baseline NLR ≥ 2.9 and PLR ≥ 148.0 may serve as predictive factors for poor OS and PFS in uHCC patients receiving Atezo-Bev-TACE treatment. Furthermore, the Atezo-Bev-TACE regimen demonstrates good efficacy and safety in the clinical management of uHCC patients.