组合激酶抑制剂和不可切除的型甲状腺癌的免疫疗法：回顾性单中心研究
Combination kinase inhibitors and immunotherapy for unresectable anaplastic thyroid carcinoma: A retrospective single-center study
影响因子:3.90000
分区:医学2区 / 牙科与口腔外科2区 肿瘤学3区
发表日期:2024 Dec
作者:
Yuntao Song, Yabing Zhang, Yanhua Bai, Tianxiao Wang, Guohui Xu, Xiao Ma, Kuangyu Fei, Bin Zhang
摘要
型甲状腺癌（ATC）很少见，但预后较差。新的治疗方法，例如多次菌酶抑制剂和选择性酪氨酸激酶抑制剂已彻底改变了对ATC的治疗，免疫疗法也表现出令人鼓舞的作用。 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用选择性或多激酶抑制剂（Dabrafenib/Trametinib，Lenvatinib或Anlotinib）与一种免疫检查点抑制剂（Pembrolizumab，sintilimab或camrelizumab）一起治疗。终点包括总生存期（OS），无进展生存期（PFS），反应评估以及R0/R1切除的可行性。中位OS（MOS）为14.0个月，12个月的存活率为55.6％。 BRAF V600E突变的MOS未达到ATC，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，有5例获得了完全反应（CR），6例患者获得了部分反应（PR）。最好的ORR为61.1％。在7/18（38.9％）患者中，手术切除是可行的。发生了一个5年级不良事件（AE）。大多数AE耐受性耐受性。通过免疫疗法作为一线治疗的激酶抑制剂可安全有效地治疗无法切除的ATC，尤其是BRAF V600E突变。
Abstract
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.