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

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.

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).