Lenvatinib is a standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, because of the high incidence of adverse events resulting from this treatment, it is not easy to maintain the dose intensity of lenvatinib, especially in Japanese patients. Although the prognostic impact of lenvatinib dose interruption has been reported, the target dose intensity of lenvatinib to optimize survival benefits remains unknown. We therefore propose a target dose intensity of lenvatinib during the first 8 weeks of treatment. We retrospectively analyzed 42 RR-DTC patients who were treated with lenvatinib for more than 8 weeks. We performed receiver operating characteristic curve analysis to determine the cut-off value of 8 weeks’ relative dose intensity (8w-RDI) to predict treatment response, and identified that the optimal cut-off value of 8w-RDI was 60% (sensitivity: 81.8%; specificity: 80.6%). Median progression-free survival (PFS) (not reached [NR] vs. 11.0 months; hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.11–0.72; p < 0.01) and overall survival (NR vs. 27.6 months; HR 0.44; 95% CI 0.11–0.91; p = 0.03) were longer in the higher 8w-RDI (≥60%) patients than in the lower 8w-RDI (<60%) patients. Multivariate analysis revealed that 8w-RDI at ≥60% was an independent prognostic factor for PFS (HR 0.29; 95% CI 0.09–0.96; p = 0.04). Targeting for ≥60% of the relative dose intensity during the first 8 weeks of lenvatinib treatment can be sufficient to achieve significant tumor shrinkage and prolong PFS in RR-DTC patients.

乐伐替尼是放射性碘难治性分化型甲状腺癌 (RR-DTC) 的标准疗法。然而，由于这种治疗导致的不良事件发生率高，维持乐伐替尼的剂量强度并不容易，尤其是在日本患者中。尽管已经报道了乐伐替尼剂量中断对预后的影响，但乐伐替尼用于优化生存获益的目标剂量强度仍然未知。因此，我们建议在治疗的前 8 周内设定乐伐替尼的目标剂量强度。我们回顾性分析了 42 名接受乐伐替尼治疗超过 8 周的 RR-DTC 患者。我们进行了受试者工作特征曲线分析，以确定 8 周相对剂量强度 (8w-RDI) 的临界值，以预测治疗反应，并确定 8w-RDI 的最佳截止值为 60%（灵敏度：81.8%；特异性：80.6%）。中位无进展生存期 (PFS)（未达到 [NR]对比11.0 个月；风险比 [HR] 0.29；95% 置信区间 [CI] 0.11–0.72；p < 0.01）和总生存期（NR vs. 27.6 个月；HR 0.44；95% CI 0.11–0.91；p = 0.03）在较高 8w-RDI（≥60%）患者中比在较低 8w-RDI 患者中更长（ <60%) 患者。多变量分析显示，≥60% 的 8w-RDI 是 PFS 的独立预后因素（HR 0.29；95% CI 0.09–0.96；p = 0.04）。在乐伐替尼治疗的前 8 周内靶向≥60% 的相对剂量强度足以实现显着的肿瘤缩小并延长 RR-DTC 患者的 PFS。