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Background and Objective <p>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.</p> Patients and Methods <p>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.</p> Results <p>Forty-one patients were enrolled between May 2020 and January 2024. AUCu/dose, but not AUCt/dose, was significantly negatively correlated with ALBI score (<i>P</i> = 0.00699). Patients with ALBI grade ≥&#xa0;2b had significantly higher AUCu/dose than those with &lt;&#xa0;2b (mean ± SD, 0.00602 ± 0.00268 vs. 0.00390 ± 0.00168 h/L, <i>P</i> = 0.0131). Child-Pugh class was associated with AUCu/dose (<i>P</i> = 0.0312); however, among Child-Pugh classification components, albumin only was associated with the AUCu/dose. Multivariate Cox proportional hazards analysis identified ALBI grade ≥&#xa0;2b as risk factor for shorter PFS (<i>P</i> = 0.0000521; hazard ratio 9.43; 95% confidence interval 3.18–28.0). ALBI grade ≥&#xa0;2b, but not Child-Pugh class, showed a significantly higher incidence of lenvatinib-induced toxicity grades ≥&#xa0;2 than ALBI grade &lt;&#xa0;2b (87.0 vs. 55.6%, <i>P</i> = 0.0357).</p> Conclusion <p>The study exploratorily found that baseline ALBI grade was associated with lenvatinib AUCu/dose and clinical responses.</p> Trial Registration Number <p>UMIN000057138 (registered on February 27, 2025)</p>

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

  • 期刊论文

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  • 发表日期：

    2026年6月23日

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  • Kosuke Suzuki,
  • Yumi Otoyama,
  • Natsumi Matsumoto,
  • Yusuke Masuo,
  • Yoko Nakajima,
  • Ikuya Sugiura,
  • Takahiro Fuji,
  • Erika Nomura,
  • Yuki Ichikawa,
  • Yuu Shimozuma,
  • Manabu Uchikoshi,
  • Momoka Hayano,
  • Mayuko Hanano,
  • Remi Murase,
  • Chika Mitomori,
  • Kiyoshi Oka,
  • Masashi Sakaki,
  • Yukio Kato,
  • Hitoshi Yoshida,
  • Ken-ichi Fujita

摘要

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)