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.
Bibliographical noteFunding Information:
Takuji Okusaka: reports research funding from Novartis Pharma, AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd, Bristol Myers K.K., and Baxter. Kenji Ikeda: reports no conflicts of interest. Masatoshi Kudo: reports advisory role for Eisai Co., Ltd, Ono, MSD, Bristol Myers Squibb, and Roche; honoraria from Eisai Co., Ltd, Bayer, MSD, Bristol Myers Squib, Lilly, and EA Pharma; grants from Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, EA Pharma, Abbvie, and Eisai Co., Ltd. Richard S. Finn: reports honoraria from Eisai and Merck. Shukui Qin reports no conflicts of interest. Kwang-Hyub Han: reports no conflicts of interest. Ann-Lii Cheng: reports honoraria from AstraZeneca, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, IPSEN Innovation, Bayer Healthcare, Merck Sharp & Dohme, Roche/Genentech, BeiGene, CSR Pharma Group, F. Hoffmann-La Roche, and IQVIA. Fabio Piscaglia: reports honoraria from Alkermes, AstraZeneca, Bayer, Bracco, Bristol Myers Squibb, Eisai, GE, Ipsen, La Force Guerbet, Roche, Siemens Healthcare, and Tiziana Life Sciences; research contract with Esaote. Masahiro Kobayashi: reports honoraria from Eisai Co., Ltd. Max W. Sung: reports honoraria from Eisai, AstraZeneca, Bayer. Minshan Chen: reports no conflicts of interest. Lucjan Wyrwicz: reports no conflicts of interest. Jung-Hwan Yoon: reports research grants from AstraZeneca, Bayer HealthCare Pharmaceuticals, Daewoong Pharmaceuticals, and Bukwang Pharmaceuticals. Zhenggang Ren: reports no conflicts of interest. Kalgi Mody: employee of Eisai Inc., Woodcliff, NJ, USA. Corina E. Dutcus: employee of Eisai Inc., Woodcliff, NJ, USA. Toshiyuki Tamai: employee of Eisai Co. Ltd, Tokyo, Japan. Min Ren: employee of Eisai Inc., Woodcliff, NJ, USA. Seiichi Hayato: employee of Eisai Co. Ltd, Tokyo, Japan. Hiromitsu Kumada: reports honoraria from MSD, Sumitomo Dainippon, AbbVie, Gilead Sciences, Inc., and Eisai.
This study was funded by Eisai Inc., Woodcliff, NJ, USA, and also by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing support was provided by Heather A. Mitchell, PhD, Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff, NJ, USA, and also by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
© 2021, The Author(s).
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