Abstract：
BACKGROUND: Treatment options for patients with differentiated thyroid cancer (DTC) who experience disease progression on lenvatinib treatment are limited. Although dose escalation of treatment with tyrosine kinase inhibitors at disease progression has been reported across cancer types, clinical significance in patients with DTC has not been investigated.
METHODS: We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose.
RESULTS: Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24 mg/day, and the median dose at initial disease progression was 10 mg/day. In the former, the median dose escalation was 6 mg/day (range: 4-12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9 months (95% confidence interval [CI] 5.71-27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4 months [95% CI 7.0-NA] vs. 3.9 months [95% CI 1.7-7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09-0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess.
CONCLUSIONS: The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC.
METHODS: We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose.
RESULTS: Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24 mg/day, and the median dose at initial disease progression was 10 mg/day. In the former, the median dose escalation was 6 mg/day (range: 4-12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9 months (95% confidence interval [CI] 5.71-27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4 months [95% CI 7.0-NA] vs. 3.9 months [95% CI 1.7-7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09-0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess.
CONCLUSIONS: The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC.
摘要：
背景：对于接受lenvatinib治疗后出现疾病进展的分化型甲状腺癌（DTC）患者的治疗选择有限。尽管已经报道了不同癌症类型的酪氨酸激酶抑制剂在疾病进展时的剂量递增。DTC患者的临床意义尚未研究。
方法：我们回顾性回顾了2011年9月至2022年6月接受lenvatinib治疗的DTC患者的疾病进展情况。我们将接受剂量递增治疗的受试者与在最初疾病进展时终止治疗的标准治疗进行了比较。通过参考先前的有效和耐受剂量来确定递增的剂量。
结果：确定了33例患者，15例剂量递增，18例lenvatinib终止。在这两组中,来伐替尼的起始剂量为24毫克/天，疾病初始进展时的中位剂量为10mg/天。在前者中,中位剂量递增为6mg/天(范围:4~12).客观反应率，按升级计算的临床获益率，剂量递增阶段的中位治疗持续时间为13.3%，73.3%,和9.9个月(95%置信区间[CI]5.71-27.6)，分别。剂量递增组的初始疾病进展的中位总生存期明显更长（中位OS：20.4个月[95％CI7.0-NA]与3.9个月[95%CI1.7-7.9]，对数秩p值；0.0004，风险比；0.22[95%CI0.09-0.55])。没有发生5级不良事件,1例患者因3级肺脓肿停药。
结论：在接受Lenvatinib治疗的DTC患者疾病进展后，剂量递增策略似乎是一种安全有效的治疗选择。
方法：我们回顾性回顾了2011年9月至2022年6月接受lenvatinib治疗的DTC患者的疾病进展情况。我们将接受剂量递增治疗的受试者与在最初疾病进展时终止治疗的标准治疗进行了比较。通过参考先前的有效和耐受剂量来确定递增的剂量。
结果：确定了33例患者，15例剂量递增，18例lenvatinib终止。在这两组中,来伐替尼的起始剂量为24毫克/天，疾病初始进展时的中位剂量为10mg/天。在前者中,中位剂量递增为6mg/天(范围:4~12).客观反应率，按升级计算的临床获益率，剂量递增阶段的中位治疗持续时间为13.3%，73.3%,和9.9个月(95%置信区间[CI]5.71-27.6)，分别。剂量递增组的初始疾病进展的中位总生存期明显更长（中位OS：20.4个月[95％CI7.0-NA]与3.9个月[95%CI1.7-7.9]，对数秩p值；0.0004，风险比；0.22[95%CI0.09-0.55])。没有发生5级不良事件,1例患者因3级肺脓肿停药。
结论：在接受Lenvatinib治疗的DTC患者疾病进展后，剂量递增策略似乎是一种安全有效的治疗选择。
