National Cancer Center Hospital, Tokyo, Japan.
Toranomon Hospital, Tokyo, Japan.
J Gastroenterol. 2021 Jun;56(6):570-580. doi: 10.1007/s00535-021-01785-0. Epub 2021 May 4.
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.
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.
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.
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.
Trial registration ID: ClinicalTrials.gov # NCT01761266.
REFLECT 是一项开放标签、3 期研究，比较了仑伐替尼与索拉非尼在不可切除肝细胞癌（uHCC）患者中的疗效和安全性。基于 2 期研究（Study 202）结果，REFLECT 中采用了基于体重的仑伐替尼给药方案，以最大程度减少因剂量相关不良反应而需要进行的剂量中断和调整。本 REFLECT 数据的事后分析按体重组评估了仑伐替尼的疗效和安全性。
该研究将未经治疗（无既往系统治疗）的 uHCC 患者随机分配接受仑伐替尼（n=476）或索拉非尼（n=475）治疗。仑伐替尼的起始剂量数据按体重分层：体重<60kg 的患者接受 8mg/天；体重≥60kg 的患者接受 12mg/天。评估总生存期（OS）、无进展生存期（PFS）、客观缓解率和安全性。
两组基于体重的仑伐替尼起始剂量组的生存结果和安全性特征似乎相似。体重<60kg 组（n=153）的中位 OS 为 13.4 个月（95%CI 10.5-15.7），而体重≥60kg 组（n=325）为 13.7 个月（95%CI 12.0-15.6）。在两组仑伐替尼组中，PFS 均为 7.4 个月（体重<60kg 组：95%CI 5.4-9.2；体重≥60kg 组：95%CI 6.9-9.0）。治疗出现的不良事件（TEAEs）需要剂量调整的比例在体重<60kg 组为 43.0%，在体重≥60kg 组为 57.5%。
REFLECT 数据的这项探索性分析表明，在 uHCC 患者中采用基于体重的仑伐替尼给药方案成功地维持了疗效，两组的 TEAEs 发生率和剂量调整率相当。
试验注册标识：ClinicalTrials.gov # NCT01761266。
