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.

• Authors: Takuji Okusaka, Kenji Ikeda, Masatoshi Kudo, Richard Finn, Shukui Qin, Kwang-Hyub Han, Ann-Lii Cheng, Fabio Piscaglia, Masahiro Kobayashi, Max Sung, Minshan Chen, Lucjan Wyrwicz, Jung-Hwan Yoon, Zhenggang Ren, Kalgi Mody, Corina Dutcus, Toshiyuki Tamai, Min Ren, Seiichi Hayato, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 56 Issue 6 Pg. 570-580 (06 2021) ISSN: 1435-5922 [Electronic] Japan
• PMID: 33948712 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Quinolines
• Sorafenib
• lenvatinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
• Body Weight (drug effects)
• Carcinoma, Hepatocellular (drug therapy)
• Dose-Response Relationship, Drug
• Female
• Humans
• Liver Neoplasms (complications, drug therapy)
• Male
• Middle Aged
• Phenylurea Compounds (adverse effects, pharmacology, therapeutic use)
• Quinolines (adverse effects, pharmacology, therapeutic use)
• Sorafenib (adverse effects, pharmacology, therapeutic use)
• Treatment Outcome