Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma

Abstract Background & Aims Nivolumab, a programmed death (PD)-1 (PD-1) inhibitor, demonstrated durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). Our retrospective analysis studied the immunobiology and potential associations between biomarkers and nivolumab outcomes in HCC. Methods Fresh and archival tumour samples from dose-escalation and -expansion phases of CheckMate 040 were analysed by immunohistochemistry and RNA sequencing to assess several inflammatory gene expression signatures, including CD274 (PD-L1), CD8A, LAG3, and STAT1. Biomarkers were assessed for association with clinical outcomes (best overall response [BOR] by blinded independent central review [BICR] per RECIST v1.1 and overall survival [OS]). Results Complete or partial tumour responses were observed in PD ligand 1 (PD–L1)–positive and –negative patients treated with nivolumab monotherapy. Median OS was 28.1 (95% CI 18.2–n.a.) vs. 16.6 months (95% CI 14.2–20.2) for patients with tumour PD-L1 ≥1% vs. Conclusions PD-1 and PD-L1 expression, biomarkers of inflammation, and inflammatory gene signatures trended with improved survival and response. While further confirmation within a larger phase III trial is needed to evaluate predictive value, these analyses indicate a role for anti-tumour immune response and treatment benefit following nivolumab treatment in HCC.