ALBI Grade is a Determinant of Lenvatinib Pharmacokinetics, Efficacy, and Toxicities in Japanese Patients with Hepatocellular Carcinoma.

BACKGROUND AND

OBJECTIVE

The doses of lenvatinib for patients with hepatocellular carcinoma (HCC) are determined using the Child-Pugh classification and body weight. Because lenvatinib is highly bound to plasma albumin (98.6%), patients with low plasma albumin levels and hepatic lenvatinib clearance may exhibit a high unbound fraction and/or concentration of lenvatinib in the plasma to alter efficacy and toxicity. This study exploratorily and prospectively examined the effects of baseline albumin-bilirubin (ALBI) on systemic exposure to unbound lenvatinib and lenvatinib clinical responses in patients with HCC.

PATIENTS AND

METHODS

Patients with HCC who received lenvatinib were enrolled. Total- and unbound-base dose-normalized area under the plasma concentration-time curve (AUCt/dose and AUCu/dose, respectively) were determined. Progression-free survival (PFS) and toxicities were evaluated.

RESULTS

Forty-one patients were enrolled between May 2020 and January 2024. AUCu/dose, but not AUCt/dose, was significantly negatively correlated with ALBI score (P = 0.00699). Patients with ALBI grade ≥ 2b had significantly higher AUCu/dose than those with < 2b (mean ± SD, 0.00602 ± 0.00268 vs. 0.00390 ± 0.00168 h/L, P = 0.0131). Child-Pugh class was associated with AUCu/dose (P = 0.0312); however, among Child-Pugh classification components, albumin only was associated with the AUCu/dose. Multivariate Cox proportional hazards analysis identified ALBI grade ≥ 2b as risk factor for shorter PFS (P = 0.0000521; hazard ratio 9.43; 95% confidence interval 3.18-28.0). ALBI grade ≥ 2b, but not Child-Pugh class, showed a significantly higher incidence of lenvatinib-induced toxicity grades ≥ 2 than ALBI grade < 2b (87.0 vs. 55.6%, P = 0.0357).

CONCLUSION

The study exploratorily found that baseline ALBI grade was associated with lenvatinib AUCu/dose and clinical responses.

TRIAL REGISTRATION NUMBER: UMIN000057138 (registered on February 27, 2025).