Perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy for resectable non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 2 trial (TD-NeoFOUR trial)

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Signal Transduction and Targeted Therapy Pub Date : 2024-10-28 DOI:10.1038/s41392-024-01992-0
Hongtao Duan, Changjian Shao, Zhilin Luo, Tianhu Wang, Liping Tong, Honggang Liu, Xin Yao, Jie Lei, Jinbo Zhao, Yuan Gao, Tao Jiang, Xiaolong Yan
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Abstract

This open-label, single-arm, phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy, followed by adjuvant sintilimab, for resectable NSCLC. Forty-five patients received anlotinib (10 mg, QD, PO, days 1–14), sintilimab (200 mg, day 1), and platinum-based chemotherapy of each three-week cycle for 3 cycles, followed by surgery within 4–6 weeks. Adjuvant sintilimab (200 mg) was administered every 3 weeks. The primary endpoint was achieving a pathological complete response (pCR). From June 10, 2021 through October 10, 2023, 45 patients were enrolled and composed the intention-to-treat population. Twenty-six patients (57.8%) achieved pCR, and 30 (66.7%) achieved major pathological response (MPR). Forty-one patients underwent surgery. In the per-protocol set (PP set), 63.4% (26/41) achieved pCR, and 73.2% achieved MPR. The median event-free survival was not attained (95% CI, 25.1-NE). During the neoadjuvant treatment phase, grade 3 or 4 treatment-related adverse events were observed in 25 patients (55.6%), while immune-related adverse events were reported in 7 patients (15.6%). We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC. Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF+ cells and CD4+Foxp3+ Treg cells, and increased perivascular CD4+ T cells, CD39+CD8+ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).

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围手术期辛替利马和新辅助安罗替尼加化疗治疗可切除的非小细胞肺癌:一项多中心、开放标签、单臂、2 期试验(TD-NeoFOUR 试验)
这项开放标签、单臂 2 期试验评估了新辅助辛替利单抗联合安罗替尼和化疗治疗可切除 NSCLC 的疗效和安全性,随后进行辛替利单抗辅助治疗。45名患者接受了安罗替尼(10毫克,QD,PO,第1-14天)、辛替利单抗(200毫克,第1天)和铂类化疗,每个化疗周期为三周,共3个周期,随后在4-6周内进行手术。辅助性辛替利马单抗(200 毫克)每 3 周注射一次。主要终点是获得病理完全反应(pCR)。从2021年6月10日到2023年10月10日,45名患者被纳入意向治疗人群。26名患者(57.8%)获得了pCR,30名患者(66.7%)获得了主要病理反应(MPR)。41名患者接受了手术治疗。在按方案治疗组(PP 组)中,63.4% 的患者(26/41)获得了 pCR,73.2% 的患者获得了 MPR。中位无事件生存期未达标(95% CI,25.1-NE)。在新辅助治疗阶段,25 名患者(55.6%)出现了 3 级或 4 级治疗相关不良事件,7 名患者(15.6%)出现了免疫相关不良事件。我们通过 mIHC 检测 NSCLC 组织中相关细胞标记物的表达,评估了血管正常化和免疫相关细胞的浸润情况。在 pCR 患者中观察到了显著的肿瘤微环境变化,包括 VEGF+ 细胞和 CD4+Foxp3+ Treg 细胞减少,血管周围 CD4+ T 细胞、CD39+CD8+ T 细胞和 M1 巨噬细胞增加。总之,围手术期辛替利马和新辅助安罗替尼加化疗可使相当一部分可切除的NSCLC患者获得pCR,并且与肿瘤微环境的深刻变化有关(ClinicalTrials.gov NCT05400070)。
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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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