Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT

Abstract

Background: REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). Based on phase 2 study (Study 202) results, body weight-based dosing for lenvatinib was used in REFLECT to minimize dose disruptions and modifications needed to address dose-related adverse events. This post hoc analysis of REFLECT data assessed lenvatinib efficacy and safety by body weight group. Methods: The study randomly administered lenvatinib (n = 476) or sorafenib (n = 475) to patients with untreated (no prior systemic therapy) uHCC. Lenvatinib starting-dose data were stratified by body weight: patients weighing < 60?kg received 8?mg/day; patients weighing ? 60?kg received 12?mg/day. Overall survival (OS), progression-free survival (PFS), objective response rate, and safety were assessed. Results: Survival outcomes and safety profiles appeared similar between the two body-weight-based lenvatinib starting-dose groups. Median OS for patients in the < 60?kg body weight group (n = 153) was 13.4?months [95% confidence interval (CI) 10.5–15.7] compared to 13.7?months (95% CI 12.0–15.6) in the ? 60?kg body weight group (n = 325). In both lenvatinib groups, PFS was 7.4?months (< 60?kg group: 95% CI 5.4–9.2; ? 60?kg group: 95% CI 6.9–9.0). Treatment-emergent adverse events (TEAEs) required dose modifications in 43.0% in the < 60?kg body weight group and 57.5% in the ? 60?kg body weight group. Conclusions: This exploratory analysis of data from REFLECT indicated that body weight-based lenvatinib dosing in patients with uHCC was successful in maintaining efficacy, with comparable rates of TEAEs and dose modifications in the two body weight groups. Clinincal trial: Trial registration ID: ClinicalTrials.gov # NCT01761266. ? 2021, The Author(s).