剂量中断对放射性碘难治性分化型甲状腺癌患者 3 期研究中仑伐替尼疗效的影响。
Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer.
机构信息
National Cancer Centre Hospital East, Kashiwa, Chiba, Japan.
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Eur J Cancer. 2019 Jan;106:61-68. doi: 10.1016/j.ejca.2018.10.002. Epub 2018 Nov 22.
BACKGROUND
In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT), lenvatinib significantly improved efficacy outcomes versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Lenvatinib-treated patients had more adverse events (AEs), which were generally managed with dose modifications, including dose interruption. This exploratory post hoc analysis investigated the impact of dose interruption on lenvatinib efficacy.
METHODS
Dose modifications were required for grade 3 or intolerable grade 2 AEs in SELECT. Lenvatinib-treated patients were dichotomised based on the duration of dose interruption relative to total treatment duration: shorter dose interruption (<10% of total treatment duration) and longer dose interruption (≥10%).
RESULTS
At the time of primary data cut-off (November 15, 2013; median follow-up, 17.1 months), the median progression-free survival (PFS) for the shorter dose-interruption group had not yet been reached, whereas median PFS for the longer dose-interruption group was 12.8 months (95% confidence interval [CI], 9.3-16.5). Compared with placebo, the hazard ratios for PFS in the shorter and longer dose-interruption groups were 0.14 (95% CI, 0.09-0.20) and 0.31 (95% CI, 0.22-0.43), respectively. In a multivariate model, dose interruption was significantly associated with lenvatinib efficacy, even after adjustment for patient characteristics.
CONCLUSIONS
Lenvatinib improved efficacy outcomes versus placebo in patients with RR-DTC, regardless of the duration of dose interruption; however, those with shorter dose interruptions had a greater magnitude of benefit versus those with longer interruptions. This analysis highlights the importance of timely management of lenvatinib toxicities to minimise dose interruptions and maximise lenvatinib efficacy in patients with RR-DTC. CLINICALTRIALS.
GOV NUMBER
NCT01321554.
背景
在 III 期 E7080（乐卫玛）治疗分化型甲状腺癌的研究（SELECT）中，乐卫玛对比安慰剂显著改善了碘难治性分化型甲状腺癌（RR-DTC）患者的疗效结局。乐卫玛治疗患者的不良事件（AE）更多，一般通过剂量调整进行管理，包括剂量中断。本探索性事后分析研究了剂量中断对乐卫玛疗效的影响。
方法
SELECT 中，需要对 3 级或不可耐受的 2 级 AE 进行剂量调整。基于剂量中断相对于总治疗持续时间的长短，将接受乐卫玛治疗的患者分为两组：剂量中断较短（＜总治疗持续时间的 10%）和剂量中断较长（≥10%）。
结果
在主要数据截止（2013 年 11 月 15 日；中位随访时间，17.1 个月）时，剂量中断较短组的中位无进展生存期（PFS）尚未达到，而剂量中断较长组的中位 PFS 为 12.8 个月（95%置信区间 [CI]，9.3-16.5）。与安慰剂相比，剂量中断较短和较长组的 PFS 风险比分别为 0.14（95%CI，0.09-0.20）和 0.31（95%CI，0.22-0.43）。在多变量模型中，即使调整了患者特征，剂量中断与乐卫玛疗效仍显著相关。
结论
无论剂量中断持续时间如何，乐卫玛均改善了 RR-DTC 患者的疗效结局，优于安慰剂；然而，与中断时间较长的患者相比，中断时间较短的患者获益更大。该分析强调了及时管理乐卫玛毒性以尽量减少剂量中断并最大化 RR-DTC 患者乐卫玛疗效的重要性。临床试验.gov 编号：NCT01321554。
Zotero 插件