甲状腺未分化癌（ATC）很少见，但预后很差。多激酶抑制剂和选择性酪氨酸激酶抑制剂等新的治疗选择彻底改变了 ATC 的治疗，免疫疗法也显示出令人鼓舞的效果。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以及新辅助治疗不可切除的 ATC 患者的疗效和安全性。这项回顾性单中心研究连续招募了 IVB 期患者和 IVC ATC 在 2021 年 6 月至 2023 年 6 月期间接受一线激酶抑制剂加免疫治疗。这些患者接受选择性或多激酶抑制剂（达拉非尼/曲美替尼、乐伐替尼或安罗替尼）联合一种免疫检查点抑制剂（派姆单抗）治疗、信迪利单抗或卡瑞利珠单抗）。终点包括总生存期 (OS)、无进展生存期 (PFS)、疗效评估和 R0/R1 切除的可行性。本次分析包括 18 名患者。中位 OS (mOS) 为 14.0 个月，12 个月生存率为 55.6%。 BRAF V600E 突变 ATC 中的 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）。在可评估的患者中，5 名患者获得完全缓解 (CR)，6 名患者获得部分缓解 (PR)。最佳 ORR 为 61.1%。 7/18 (38.9%) 的患者可以进行手术切除。发生 1 起 5 级不良事件 (AE)。大多数 AE 耐受性良好。联合激酶抑制剂与免疫疗法作为一线治疗对于治疗不可切除的 ATC 是安全有效的，尤其是 BRAF V600E 突变的患者。版权所有 © 2024 Elsevier Ltd。保留所有权利。

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.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.Copyright © 2024 Elsevier Ltd. All rights reserved.