Department of Head and Neck Surgery, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China.
Department of Pathology, Peking University Cancer Hospital and Institute. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China.
Oral Oncol. 2024 Dec;159:107067. doi: 10.1016/j.oraloncology.2024.107067. Epub 2024 Oct 11.
Anaplastic thyroid carcinoma (ATC) is rare but has a very poor prognosis. New therapeutic options such as multikinase inhibitors and selective tyrosine kinase inhibitors have revolutionized the treatment of ATC, with immunotherapy also showing encouraging effects. This study evaluated the efficacy and safety of kinase inhibitors combined with an anti-PD-1 inhibitor as first-line treatment, as well as in the neoadjuvant setting for patients with unresectable ATC.
MATERIALS & METHODS: This retrospective single-center study recruited consecutive patients with stage IVB and IVC ATC who received first-line kinase inhibitors plus immunotherapy between June 2021 and June 2023. The patients were treated with either selective or multi-kinase inhibitors (dabrafenib/trametinib, lenvatinib, or anlotinib) in combination with one immune checkpoint inhibitor (pembrolizumab, sintilimab, or camrelizumab). The endpoints included overall survival (OS), progression-free survival (PFS), response evaluation, and feasibility of R0/R1 resection.
Eighteen patients were included in this analysis. The median OS (mOS) was 14.0 months and the 12-month survival rate was 55.6 %. The mOS in BRAF V600E mutated ATC was not reached, significantly longer than non-BRAF V600E mutated ATC (4.0 months [95 %CI, 1.1-6.9], p = 0.049). Among evaluable patients, 5 achieved a complete response (CR) and 6 patients achieved partial response (PR). The best ORR was 61.1 %. Surgical resection was feasible in 7/18 (38.9 %) patients. One grade 5 adverse event (AE) occurred. Most AEs were well tolerated.
Combination kinase inhibitors with immunotherapy as first-line therapy are safe and effective for the treatment of unresectable ATC, especially with BRAF V600E mutation.
间变性甲状腺癌（ATC）较为罕见，但预后极差。新型治疗方法，如多激酶抑制剂和选择性酪氨酸激酶抑制剂的出现，彻底改变了 ATC 的治疗方式，免疫疗法也显示出了令人鼓舞的效果。本研究评估了激酶抑制剂联合抗 PD-1 抑制剂作为一线治疗方案，以及用于不可切除 ATC 患者新辅助治疗的疗效和安全性。
本回顾性单中心研究纳入了 2021 年 6 月至 2023 年 6 月期间接受一线激酶抑制剂联合免疫治疗的 IVB 期和 IVC 期 ATC 连续患者。患者接受选择性或多激酶抑制剂（达拉非尼/曲美替尼、仑伐替尼或安罗替尼）联合一种免疫检查点抑制剂（帕博利珠单抗、信迪利单抗或卡瑞利珠单抗）治疗。主要终点包括总生存期（OS）、无进展生存期（PFS）、反应评估和 R0/R1 切除的可行性。
本研究共纳入 18 例患者。中位 OS（mOS）为 14.0 个月，12 个月生存率为 55.6%。BRAF V600E 突变 ATC 的 mOS 未达到，明显长于非 BRAF V600E 突变 ATC（4.0 个月[95%CI，1.1-6.9]，p=0.049）。在可评估患者中，5 例达到完全缓解（CR），6 例达到部分缓解（PR）。最佳 ORR 为 61.1%。18 例患者中有 7 例（38.9%）可行手术切除。1 例发生 5 级不良事件（AE）。大多数 AE 均可耐受。
联合激酶抑制剂和免疫疗法作为一线治疗方案，治疗不可切除的 ATC 安全有效，尤其是针对 BRAF V600E 突变患者。
