Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.
Department of Otolaryngology and Head and Neck Surgery, Jichi Medical University, Tochigi, Japan.
Int J Clin Oncol. 2024 Oct;29(10):1435-1443. doi: 10.1007/s10147-024-02581-5. Epub 2024 Jul 23.
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.
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.
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.
The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC.
接受仑伐替尼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。尽管在各种癌症类型中均有报道在疾病进展时增加酪氨酸激酶抑制剂的剂量，但尚未在 DTC 患者中进行过临床意义的研究。
我们回顾性分析了 2011 年 9 月至 2022 年 6 月期间接受仑伐替尼治疗后出现疾病进展的 DTC 患者。我们比较了接受剂量递增治疗和初始疾病进展时终止标准治疗的患者。递增剂量参考之前有效的和可耐受的剂量来决定。
共确定了 33 例患者，其中 15 例接受剂量递增，18 例终止仑伐替尼治疗。两组患者仑伐替尼的起始剂量均为 24mg/天，初始疾病进展时的中位剂量为 10mg/天。前者中位剂量递增为 6mg/天（范围：4-12）。剂量递增组的客观缓解率、临床获益率和剂量递增阶段的中位治疗持续时间分别为 13.3%、73.3%和 9.9 个月（95%置信区间[CI]：5.71-27.6）。剂量递增组从初始疾病进展的中位总生存期明显长于对照组（中位 OS：20.4 个月[95%CI：7.0-NE]vs.3.9 个月[95%CI：1.7-7.9]，对数秩检验，p 值<0.0004，风险比为 0.22[95%CI：0.09-0.55]）。没有 5 级不良事件，有 1 例患者因 3 级肺脓肿而停药。
在接受仑伐替尼治疗的 DTC 患者中，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。
