Inflammatory markers tied to better HCC outcomes after nivolumab treatment

Following treatment with nivolumab, a programmed death (PD)-1 inhibitor, the expression of inflammatory markers seems to correlate with better survival and treatment response in hepatocellular carcinoma (HCC) patients, a recent study has shown. This suggests that antitumour inflammatory mechanisms play a role in the action of nivolumab.

A total of 195 pretreatment tumour samples were used in the current analysis. Immunohistochemistry and RNA sequencing were performed to measure biomarkers of inflammation, such as PD-1, PD-ligand 1 (PD-L1), and STAT1, LAG3, and CD8A genes. All samples were from patients who had received a 3-mg/kg dose of nivolumab.

Compared with samples that had PD-L1 expression <1 percent, those with PD-L1 ≥1 percent saw a numerically higher objective response rate (28 percent vs 16 percent). In addition, the proportions of patients who achieved complete (6 percent vs 4 percent) and partial (22 percent vs 12 percent) response were also greater in the PD-L1 ≥1-percent subgroup.

A higher PD-L1 was significantly also associated with better overall survival (OS; p=0.032). Patients with PD-L1 expression ≥1 percent had a median OS of 28.1 months, significantly longer than the 16.6-month survival in counterparts with PD-L1 <1 percent. Higher PD-1 likewise seemed to have a significant effect on OS but was only borderline significant (p=0.05).

In addition, a four-gene signature including markers of inflammation showed significant associations with better objective response rate to treatment (p=0.05) and OS (p=0.01). This gene signature included the CD8A, LAG3, and STAT1 genes, as well as the CD274 gene, which encodes for PD-L1.

“Future biomarker studies may increase understanding of the key molecular drivers of antitumour immunity and continue to support the connection between the mechanism of action of nivolumab and efficacy in HCC,” the researchers said, adding that “larger controlled studies in HCC could also help evaluate the potential predictive/prognostic values of inflammatory biomarkers for nivolumab treatment response.”