Chrome Extension
WeChat Mini Program
Use on ChatGLM
VIPCreated with Sketch.

    • Final Survival Outcomes and Exploratory Biomarker Analysis from the Randomized, Phase 2 Neoscore Trial: Two Versus Three Cycles of Neoadjuvant Sintilimab Plus Chemotherapy for Resectable Non-Small Cell Lung Cancer.

    Fuming Qiu,Junqiang Fan,Miner Shao,Jie Yao,Lufeng Zhao,Ling Zhu,Baizhou Li,Yanbiao Fu,Lili Li,Mengyao Chen, Xinyi Zhang, Bangyi Zhou, Yixin Zhang,Huiying Liu,Jinglian Tu,Xiaoke Chen,Zuqun Wu,Zexin Chen

    Journal of Clinical Oncology（2024）

    Second Affiliated Hospital of Zhejiang University

    Cited 0|Views6
    Abstract
    8048 Background: In the neoSCORE trial (NCT04459611), three cycles of neoadjuvant sintilimab plus chemotherapy achieved a numerically higher major pathological response (MPR) rate compared to two cycles. However, the relationship between MPR and survival in resectable non-small cell lung cancer (NSCLC) patients receiving neoadjuvant immunotherapy is not currently fully elucidated. Furthermore, reliable predictive biomarkers are still lacking. Here, we report the survival and biomarker results of the study. Methods: Eligible patients with stage IB-IIIA resectable NSCLC were randomized 1:1 to receive either two or three cycles of neoadjuvant treatment with sintilimab (200mg) plus platinum-doublet chemotherapy (Q3W). After surgery, patients received totally four doses of perioperative immuno-chemotherapy. The primary endpoint was the MPR rate. Secondary endpoints included the complete pathological response (pCR) rate, objective response rate (ORR), 2-year disease-free survival (DFS) rate, 2-year overall survival (OS) rate, and safety. Tumor samples (n = 19) were obtained for immune biomarker analysis via mass cytometry time of flight (CyTOF). Multiplexed immunofluorescence (mIF) was performed on FFPE tumor samples (n = 42). Results: At the data cutoff (15/1/2024), 55 patients received neoadjuvant immuno-chemotherapy and underwent surgical resection, with a median follow-up of 36.1 months. DFS (HR = 1.25, P= 0.595) and OS (HR = 0.88, P= 0.830) were similar between the two-cycle and three-cycle groups. The median DFS and OS were not reached in both groups. The 2-year DFS rate in the two-cycle and three-cycle groups were 76.9% and 65.5%, and the 2-year OS rates were 84.6% and 86.2%, respectively. In a multivariable Cox analysis including clinical characteristics, therapy, and pathological response, only MPR was significantly associated with longer DFS (HR = 0.32, P= 0.044). The AUC for the percentage of residual viable tumor in predicting DFS was 0.649 ( P= 0.061). CyTOF analysis demonstrated that increased infiltration of CD8+CD38+CD103- T cells after neoadjuvant immuno-chemotherapy was significantly associated with MPR ( P= 0.035). The mIF confirmed that patients achieving MPR showed higher frequencies of CD8+CD38+CD103- T cells than those without MPR ( P= 0.005). Additionally, patients with higher proportions of CD8+CD38+CD103- T cells had a trend towards improved DFS (HR = 0.39, P= 0.061) and OS (HR = 0.45, P= 0.259). Conclusions: Neoadjuvant sintilimab plus chemotherapy was feasible and demonstrated a robust and persistent survival benefit in resectable NSCLC. MPR was associated with improved DFS. Increased CD8+CD38+CD103- T cells were associated with MPR, with a trend towards a better survival benefit, suggesting that it could be a promising predictive biomarker. Clinical trial information: NCT04459611 .
    More
    Translated text
    求助PDF
    上传PDF
    View via Publisher
    Bibtex
    AI Read Science
    AI Summary
    AI Summary is the key point extracted automatically understanding the full text of the paper, including the background, methods, results, conclusions, icons and other key content, so that you can get the outline of the paper at a glance.
    Example
    Background
    Key content
    Introduction
    Methods
    Results
    Related work
    Fund
    Key content
    • Pretraining has recently greatly promoted the development of natural language processing (NLP)
    • We show that M6 outperforms the baselines in multimodal downstream tasks, and the large M6 with 10 parameters can reach a better performance
    • We propose a method called M6 that is able to process information of multiple modalities and perform both single-modal and cross-modal understanding and generation
    • The model is scaled to large model with 10 billion parameters with sophisticated deployment, and the 10 -parameter M6-large is the largest pretrained model in Chinese
    • Experimental results show that our proposed M6 outperforms the baseline in a number of downstream tasks concerning both single modality and multiple modalities We will continue the pretraining of extremely large models by increasing data to explore the limit of its performance
    Upload PDF to Generate Summary
    Must-Reading Tree
    Example
    Generate MRT to find the research sequence of this paper
    Data Disclaimer
    The page data are from open Internet sources, cooperative publishers and automatic analysis results through AI technology. We do not make any commitments and guarantees for the validity, accuracy, correctness, reliability, completeness and timeliness of the page data. If you have any questions, please contact us by email: report@aminer.cn
    Chat Paper
    【要点】：研究揭示了新辅助 sintilimab 加化疗治疗可切除非小细胞肺癌（NSCLC）的生存结果及生物标志物分析，发现主要病理学反应（MPR）与无病生存期（DFS）相关，CD8+CD38+CD103- T细胞可能与预后改善有关。
    

    【方法】：患者在术前接受两周期或三周期新辅助 sintilimab（200mg）加铂双药化疗，术后进行四剂围手术期免疫化疗，通过CyTOF和多重免疫荧光技术对肿瘤样本进行分析。
    

    【实验】：55名患者接受了新辅助免疫化疗并进行了手术切除，中位随访36.1个月，使用CyTOF和mIF技术对19个和42个肿瘤样本进行了免疫生物标志物分析，DFS和OS在两组间相似，但MPR与DFS显著相关，CD8+CD38+CD103- T细胞的增加与MPR有关，并可能预示更好的生存获益。