Dynamics of the neutrophil-to-lymphocyte ratio during lenvatinib treatment for unresectable hepatocellular carcinoma

Lenvatinib is an approved therapy for advanced hepatocellular carcinoma (HCC). Recently, immune checkpoint inhibitors have been approved as frontline chemotherapies for HCC, and the tumor immune microenvironment (TIME) has been demonstrated to significantly affect HCC treatment. The neutrophil-to-lymphocyte ratio (NLR) is associated with the TIME, and the dynamics of the NLR are associated with prognosis or treatment efficacy in various cancer types. The present study investigated the dynamics of the TIME using the NLR in 101 patients with HCC treated with lenvatinib. Immunostaining for CD8+ tumor-infiltrating lymphocytes (TILs) was also performed in 9 patients who underwent liver tumor biopsy prior to subsequent chemotherapy for progression or discontinuation due to adverse events on lenvatinib treatment. The NLR values measured at the start of treatment (SOT), after 1 month of treatment and after 3 months of treatment were 2.78 +/- 2.20, 2.61 +/- 1.86 and 2.66 +/- 2.36, respectively (P=0.733). Among the patients with no reduction in the initial dose, there was no significant difference between the NLR after 1 month (2.34 +/- 0.25) and that at the SOT (2.86 +/- 2.33) (P=0.613). In patients who achieved a complete or partial response, the NLR at the time of the best tumor response was 1.65 +/- 0.56, which was significantly lower than that at the SOT (2.05 +/- 0.78) (P=0.023). In patients who did not respond to lenvatinib, the NLR at the time of disease progression was 3.68 +/- 3.19, which was significantly higher than that at the SOT (2.78 +/- 1.79) (P=0.043). Overall, 5 out of the 6 patients who did not respond to lenvatinib had low CD8+ TIL counts at disease progression. Although the present study included a limited number of patients, the NLR was associated with the therapeutic effects of lenvatinib. These findings suggest the potential of lenvatinib as an immunomodulator.