不可切除性未分化甲状腺癌的联合激酶抑制剂与免疫治疗：一项回顾性单中心研究
Combination kinase inhibitors and immunotherapy for unresectable anaplastic thyroid carcinoma: A retrospective single-center study
DOI 原文链接
用sci-hub下载
如无法下载，请从 Sci-Hub 选择可用站点尝试。
影响因子:3.9
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
DOI:
10.1016/j.oraloncology.2024.107067
摘要
未分化甲状腺癌（ATC）虽少见，但预后极差。多靶点酶抑制剂和选择性酪氨酸激酶抑制剂等新型治疗方案已革新了ATC的治疗方式，免疫治疗也显示出鼓舞人心的效果。本研究评估了联合激酶抑制剂与抗PD-1抑制剂作为一线治疗及新辅助治疗不可切除性ATC的疗效与安全性。该回顾性单中心研究招募了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期连续患者。患者使用选择性或多靶点酶抑制剂（达拉菲尼/曲美替尼、雷姆妥昔尼或安洛替尼）联合一种免疫检查点抑制剂（派姆单抗、信迪利单抗或卡瑞利单抗）。主要观察指标包括总生存期（OS）、无进展生存期（PFS）、反应评估及R0/R1切除的可行性。共纳入18例患者。中位OS为14.0个月，12个月生存率为55.6%。BRAF V600E突变患者的中位OS尚未达到，显著长于非突变患者（4.0个月 [95% CI 1.1-6.9]，p=0.049）。在可评估患者中，5例达完全缓解（CR），6例达部分缓解（PR），最佳反应率（ORR）为61.1%。7例患者（38.9%）实现了手术切除。发生1例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治疗作为一线方案对于不可切除的ATC安全有效，尤其适用于BRAF V600E突变患者。
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.