A phase I pharmacokinetic study of lenvatinib in Chinese patients with unresectable hepatocellular carcinoma

Future Oncol. 2022 Jul;18(22):2413-2424. doi: 10.2217/fon-2022-0229. Epub 2022 Jun 8.

Abstract

Aim: This phase I study assessed the pharmacokinetic profile, safety and antitumor activity of lenvatinib in Chinese patients with unresectable hepatocellular carcinoma. Materials & methods: Bodyweight-based lenvatinib dosing was administered (patients <60 kg: 8 mg/day, n = 13; patients ≥60 kg: 12 mg/day, n = 12). Pharmacokinetic sampling was performed during the first cycle. Efficacy and safety were assessed. Results: There was considerable overlap between individual exposure values at steady-state in the 8 and 12 mg groups. The most common adverse events were increased blood bilirubin and decreased platelet count (48.0%). Two patients had partial responses, and 16 patients attained stable disease. Conclusion: No significant pharmacokinetic differences between dose groups were detected. Lenvatinib was tolerable, showing promising antitumor activities in Chinese patients with unresectable hepatocellular carcinoma.

Trial registration: ClinicalTrials.gov NCT02953743.

Keywords: Chinese patients; bodyweight dosing; hepatocellular carcinoma; kinase inhibitor; lenvatinib; pharmacokinetics.

Plain language summary

Hepatocellular carcinoma (HCC; liver cancer) is common in Chinese patients. Lenvatinib is a drug approved to treat HCC, and patients with higher bodyweights are given a higher dose than patients with lower bodyweights. This trial in Chinese patients with HCC looked at lenvatinib pharmacokinetics (what the body does to a drug) after one dose and multiple doses, and at lenvatinib’s antitumor activity and side effects. Meaningful differences in pharmacokinetics between the higher and lower doses after a single dose or multiple doses of daily lenvatinib were not observed. Lenvatinib partially shrank the tumors of 2 out of 21 patients whose tumors were assessed. The side effects seen matched those from other studies of lenvatinib in HCC and other cancers. ClinicalTrial Registration: NCT02953743 (ClinicalTrials.gov).

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • China / epidemiology
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Phenylurea Compounds / adverse effects
  • Quinolines* / adverse effects

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Quinolines
  • lenvatinib

Associated data

  • ClinicalTrials.gov/NCT02953743