Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
Journal of gastroenterology - 56(2021), 6 vom: 23. Juni, Seite 570-580 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Okusaka, Takuji [VerfasserIn] |
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| Links: |
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| Themen: |
9ZOQ3TZI87 |
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| Anmerkungen: |
Date Completed 03.12.2021 Date Revised 14.12.2021 published: Print-Electronic ClinicalTrials.gov: NCT01761266 Citation Status MEDLINE |
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| doi: |
10.1007/s00535-021-01785-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325016526 |
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| 100 | 1 | |a Okusaka, Takuji |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 03.12.2021 | ||
| 500 | |a Date Revised 14.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01761266 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CLININCAL TRIAL: Trial registration ID: ClinicalTrials.gov # NCT01761266 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Body weight | |
| 650 | 4 | |a Dosing | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Lenvatinib | |
| 650 | 4 | |a REFLECT | |
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| 650 | 7 | |a lenvatinib |2 NLM | |
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| 700 | 1 | |a Ikeda, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Kudo, Masatoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Finn, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Shukui |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Kwang-Hyub |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Ann-Lii |e verfasserin |4 aut | |
| 700 | 1 | |a Piscaglia, Fabio |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Masahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Sung, Max |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Minshan |e verfasserin |4 aut | |
| 700 | 1 | |a Wyrwicz, Lucjan |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Jung-Hwan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Zhenggang |e verfasserin |4 aut | |
| 700 | 1 | |a Mody, Kalgi |e verfasserin |4 aut | |
| 700 | 1 | |a Dutcus, Corina |e verfasserin |4 aut | |
| 700 | 1 | |a Tamai, Toshiyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Hayato, Seiichi |e verfasserin |4 aut | |
| 700 | 1 | |a Kumada, Hiromitsu |e verfasserin |4 aut | |
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