Risk factors for lenvatinib-induced hypertension in patients with hepatocellular carcinoma: A retrospective study

Br J Clin Pharmacol. 2025 Mar;91(3):894-902. doi: 10.1111/bcp.16337. Epub 2024 Nov 20.

Abstract

Aims: Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). LEN therapy for HCC is associated with a high incidence of adverse events, including hypertension (HTN). However, the risk factors associated with LEN therapy remain unclear. This study investigated the incidence of LEN-induced HTN (LENiHTN), and the relationship between HTN incidence and patient demographics in patients with HCC receiving LEN therapy.

Methods: This was a single-centre, retrospective study of patients with HCC who received LEN therapy between 19 April 2018 and 30 September 2020. The observation period was from 1 week before the start to 1 month after the end of LEN administration.

Results: Seventy-five patients with HCC were enrolled. Any grade LENiHTN was found in 74.7% of patients. Among patients with LENiHTN, the use of 2 or more antihypertensive agents before starting LEN was less common (P = .007); serum potassium (K) and albumin-bilirubin score (ALBI) were lower (P = .013 and 0.038, respectively); and albumin (Alb) was higher (P = .025). The cut-off values of K, Alb and ALBI for HTN were estimated at 4.1 mEq L-1, 3.1 g dL-1 and -1.736, respectively. In the multivariable analysis, low K (adjusted HR: 2.078) and low ALBI (adjusted HR: 2.845) were independent risk factors for LENiHTN.

Conclusion: Low K, high Alb and low ALBI were independent risk factors for LENiHTN. Systematic evaluation of HTN risk and early intervention for HTN prevention among high-risk patients can markedly enhance LEN therapy efficacy and use.

Keywords: albumin; albumin–bilirubin score; hepatocellular carcinoma; lenvatinib; potassium.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / adverse effects
  • Carcinoma, Hepatocellular* / drug therapy
  • Female
  • Humans
  • Hypertension* / chemically induced
  • Hypertension* / epidemiology
  • Incidence
  • Liver Neoplasms* / drug therapy
  • Male
  • Middle Aged
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Retrospective Studies
  • Risk Factors

Substances

  • lenvatinib
  • Quinolines
  • Phenylurea Compounds
  • Antihypertensive Agents
  • Antineoplastic Agents
  • Protein Kinase Inhibitors