Tislelizumab (TIS) is a specific monoclonal antibody targeting programmed cell death protein 1 that demonstrated non-inferior overall survival (OS) compared to sorafenib (SOR) in phase 3 RATIONALE-301 trial (NCT03412773). They used it as first-line monotherapy for unresectable hepatocellular carcinoma (HCC). The median OS was 15.9 months for TIS and 14.1 months for SOR, with a hazard ratio (HR) of 0.85. The safety profile of TIS was favorable. In this exploratory analysis, certain biomarkers, including albumin-bilirubin (ALBI) grade, platelet count, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), were investigated as potential prognostic factors affecting OS in the first-line treatment of unresectable HCC in the RATIONALE-301 trial.

Adults who did not receive systemic therapy and had histologically confirmed HCC at Barcelona Clinic Liver Cancer Stage C or Stage B that was unsuitable for or had progressed after loco-regional therapy, and had a Child-Pugh score of A, were eligible for this study. These patients were required to have at least one measurable lesion according to RECIST v1.1 and an ECOG performance status of 0 or 1. They were randomly assigned in a 1:1 ratio to receive either TIS (200 mg intravenously every three weeks) or SOR (400 mg orally twice daily) until disease progression, intolerable side effects, or withdrawal from the study. The primary endpoint of the study was overall survival (OS).

A total of 674 patients were included in the study, with 342 patients receiving TIS and 332 patients receiving SOR. The minimum follow-up period at the data cutoff date (July 11, 2022) was 33 months. The demographic and baseline characteristics related to biomarkers were generally well-balanced between the two treatment arms. In the biomarker subgroups, a numerically longer median overall survival (mOS) of at least 2 months was observed in patients with ALBI grade 1 compared to grade 2, NLR (neutrophil-lymphocyte ratio) of ≤3 compared to >3 for both TIS and SOR and PLR (platelet-lymphocyte ratio) of ≤141 compared to >141 for TIS. The difference in mOS between the biomarker cutoffs was smaller (<2 months) for platelet count thresholds, indicating a limited prognostic value for this particular biomarker. In addition, TIS demonstrated a numerically longer overall survival compared to SOR in the following subgroup categories: ALBI grade 1, PLR ≤141, and NLR ≤3.

Based on this analysis, the ALBI grade, PLR, and NLR biomarkers may have prognostic value for overall survival (OS) regardless of the treatment received. In addition, the data showed that TIS had numerically better median OS than SOR for patients with a PLR of ≤141 and an NLR of ≤3. This finding suggests that there may be a more significant benefit for patients with a more favorable balance between systemic inflammation and immunity.