Clinical significance of neutrophil-to-lymphocyte ratio dynamics during cabozantinib therapy in unresectable hepatocellular carcinoma.

e16240 Background: Neutrophil-to-lymphocyte ratio (NLR) dynamics have been reported as prognostic biomarkers in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitor (ICI)–based regimens and other molecular targeted agents. However, the clinical relevance of NLR dynamics during cabozantinib therapy remains unclear, particularly in patients previously exposed to ICIs. Methods: We retrospectively analyzed 62 patients with unresectable HCC treated with cabozantinib. Baseline NLR was calculated prior to treatment initiation. Early on-treatment NLR dynamics were assessed at 4 weeks using the log-transformed NLR ratio (week 4/baseline). Associations between baseline NLR, NLR dynamics, and progression-free survival (PFS) and overall survival (OS) were evaluated. Results: The median age was 75 years, 77% were male, and 77% had Child–Pugh class A liver function. BCLC stage C disease accounted for 61% of patients. Cabozantinib was administered as second- or third-line therapy in 61% of patients and as fourth-line or later therapy in 39%. Prior ICI-based regimens had been used in 87% of patients. With a median follow-up of 9.7 months, median PFS and OS were 3.8 months (95% CI, 3.0–4.9) and 15.8 months (95% CI, 9.2–19.1), respectively. Baseline NLR was not significantly associated with PFS or OS. At 4 weeks, the median log-transformed NLR ratio was −0.13 (IQR, −0.41 to 0.16). However, early NLR dynamics did not stratify PFS or OS. These findings were consistent across treatment lines. Conclusions: These results suggest that the prognostic relevance of NLR dynamics during cabozantinib therapy may differ from that observed with other systemic treatments for HCC. From a clinical perspective, baseline or early on-treatment NLR may be less informative for patient stratification during cabozantinib therapy.