Onaga Ryutaro, Enokida Tomohiro, Tanaka Nobukazu, Hoshi Yuta, Kishida Takuma, Kuboki Ryo, Sato Masanobu, Takeshita Naohiro, Tanaka Hideki, Fujisawa Takao, Okano Susumu, Nishino Hiroshi, Ito Makoto, Tahara Makoto
Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Otolaryngology and Head and Neck Surgery, Jichi Medical University, Tochigi, Japan.
Thyroid. 2025 Jul;35(7):781-788. doi: 10.1089/thy.2025.0040. Epub 2025 Jun 9.
Although accumulated experience with lenvatinib in patients with differentiated thyroid cancer (DTC) and progressive radioactive iodine (RAI)-refractory disease has been used to improve management strategies for this disease, findings regarding the actual clinical picture and long-term observation data are insufficient. We conducted a retrospective cohort study of patients with DTC who received lenvatinib treatment from 2011 to 2022 at the National Cancer Center Hospital East, Japan. The patients were treated under the following treatment and management policies (1) starting dose at 24 mg/day, (2) schedule modification according to individual adverse events status (planned drug holidays), (3) dose escalation of lenvatinib, and (4) local therapy at disease progression, if applicable. This is a retrospective cohort study, although some patients were enrolled in a prospective clinical trial (NCT01321554 and UMIN000022243). Of 91 patients, 59 (64.8%) had papillary carcinoma and 22 (24.2%) had follicular carcinoma. Best overall response in all patients was 60.4% (partial response in 55 and complete response in 0). With a median observation period of 2.9 years (range, 0.1-12.4; interquartile range, 1.7-4.6) under supportive management, including the planned drug holidays ( = 72, 79.1%), dose escalation of lenvatinib at systemic disease progression ( = 21, 23.1%), and local therapy for oligoprogressive disease ( = 11, 12.1%), median progression-free survival and overall survival were 2.4 years (95% confidence interval [CI] 1.9-3.3) and 5.1 years (95% CI 3.3-6.7), respectively. At the time of data cutoff, 19.8% had discontinued lenvatinib treatment due to adverse events, although no adverse event was grade 5. In patients with RAI-refractory DTC treated with lenvatinib, careful treatment optimization and management of adverse events contribute to a favorable, durable prognosis.
尽管在分化型甲状腺癌（DTC）和进展性放射性碘（RAI）难治性疾病患者中使用乐伐替尼积累的经验已用于改进该疾病的管理策略，但关于实际临床情况和长期观察数据的研究结果仍不充分。我们对2011年至2022年在日本国立癌症中心东医院接受乐伐替尼治疗的DTC患者进行了一项回顾性队列研究。患者按照以下治疗和管理策略进行治疗：（1）起始剂量为24毫克/天；（2）根据个体不良事件状态调整治疗计划（计划性药物假期）；（3）乐伐替尼剂量递增；（4）疾病进展时进行局部治疗（如适用）。这是一项回顾性队列研究，尽管部分患者纳入了一项前瞻性临床试验（NCT01321554和UMIN000022243）。91例患者中，59例（64.8%）为乳头状癌，22例（24.2%）为滤泡状癌。所有患者的最佳总体缓解率为60.4%（部分缓解55例，完全缓解0例）。在包括计划性药物假期（n = 72，79.1%）、全身疾病进展时乐伐替尼剂量递增（n = 21，23.1%）和寡进展性疾病局部治疗（n = 11，12.1%）在内的支持性管理下，中位观察期为2.9年（范围0.1 - 12.4年；四分位间距1.7 - 4.6年），中位无进展生存期和总生存期分别为2.4年（95%置信区间[CI] 1.9 - 3.3）和5.1年（95% CI 3.3 - 6.7）。在数据截止时，19.8%的患者因不良事件停用了乐伐替尼治疗，尽管无不良事件为5级。在接受乐伐替尼治疗的RAI难治性DTC患者中，仔细优化治疗和管理不良事件有助于获得良好、持久的预后。
