221P - Peripheral T cell activation phenotype predicts clinical outcomes of atezolizumab-bevacizumab therapy in unresectable hepatocellular carcinoma

Background

Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated superior efficacy to sorafenib, thereby becoming the new standard first-line treatment in patients with unresectable hepatocellular carcinoma (HCC). However, there is a lack of reliable biomarkers that could predict clinical outcomes of Ate/Bev. In this study, we aimed to assess the clinical and immunological implications of peripheral T-cell activation phenotype as a biomarker in patients with HCC treated with Ate/Bev.

Methods

This study prospectively enrolled 106 patients with unresectable HCC treated with Ate/Bev (discovery cohort: 50 patients from one center; validation cohort: 56 patients) as the first-line systemic treatment in three tertiary cancer centers in Korea. Baseline blood samples were analyzed using multiplex flow cytometry.

Results

The optimal cut-off value for baseline peripheral T-cell activation phenotype (IFN-γ⁺TNF-α⁺), 2.50%, was determined using maximally selected rank statistics. In the discovery cohort, the patients with high-peripheral T-cell activation phenotype at baseline had an increased objective response rate (ORR) than those with low activation levels (15.4% vs. 35.1%). Moreover, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with high-peripheral T-cell activation phenotype than those with low levels (hazard ratio [HR], 0.37; 95% CI, 0.18–0.79; P = 0.008 for PFS; HR, 0.18; 95% CI, 0.07–0.41; P < 0.001 for OS). In the validation cohort, these findings were consistently observed. The patients with high-peripheral T cell activation phenotype at baseline were associated with a higher ORR (15.0% vs. 38.9%) and longer PFS (HR, 0.43; 95% CI, 0.22–0.85; P = 0.012) and OS (HR, 0.41; 95% CI, 0.18–0.96; P = 0.035) compared with those with low activation levels.

Conclusions

Highly activated peripheral T-cell phenotype was associated with favorable clinical benefit in patients with unresectable HCC treated with Ate/Bev. Therefore, peripheral T-cell activation phenotypes could be used as a potential predictor of Ate/Bev treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This work was supported by the National Research Foundation of Korea [NRF] grants funded by the Korean government [MSIT] [NRF-2023R1A2C2004339 to HJC, NRF-2023R1A2C2006375 to CK].

Disclosure

C. Kim: Financial Interests, Personal, Advisory Board: Roche, ONO, MSD, BMS, Oncocross, Virocure. H. Chon: Financial Interests, Personal, Advisory Board: Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, Sillajen, Menarini, GreenCross Cell. All other authors have declared no conflicts of interest.