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Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial
Nature Medicine ( IF 58.7 ) Pub Date : 2023-07-24 , DOI: 10.1038/s41591-023-02469-3
Jun Yin 1 , Jingnan Yuan 2, 3, 4 , Yunjin Li 2, 4 , Yong Fang 1 , Ruoxi Wang 2 , Heng Jiao 1 , Han Tang 1 , Shaoyuan Zhang 1 , Siyun Lin 1 , Feng Su 1 , Jianmin Gu 1 , Tian Jiang 1 , Dong Lin 1 , Zhiliang Huang 1, 5 , Chaoxiang Du 1, 5 , Kui Wu 2, 3, 4 , Lijie Tan 1, 5 , Qing Zhou 2, 3, 4
Affiliation  

Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results of a phase 1b trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility; secondary endpoints included pathologic complete response (pCR) and OS. Our data showed the primary endpoints of safety and feasibility had been met. Common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. Of the 30 patients enrolled in the trial, 25 underwent successful resection without surgery delay and 24% had major pathologic responses including a pCR rate of 8%. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was a hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC.



中文翻译:

新辅助阿德布雷利单抗治疗局部晚期可切除食管鳞状细胞癌:1b 期试验

在局部晚期食管鳞状细胞癌(ESCC)中,新辅助免疫治疗的总体生存(OS)益处仍然难以捉摸。在这里,我们报告了在可切除食管癌中使用阿德布雷利单抗进行新辅助 PD-L1 阻断的 1b 期试验的结果。患者接受了两剂阿德布雷单抗新辅助治疗,然后接受手术。主要终点是安全性和可行性;次要终点包括病理完全缓解 (pCR) 和 OS。我们的数据显示安全性和可行性的主要终点已经得到满足。常见的治疗相关不良事件是厌食(32%)和疲劳(16%),没有 3 级或以上不良事件。在参加该试验的 30 名患者中,25 名患者成功进行了切除,且没有延误手术,24% 的患者出现了主要病理反应,其中 pCR 率为 8%。2 年 OS 为 92%。有反应的患者具有免疫丰富的肿瘤微环境表型,而无反应的患者在基线时具有更大的癌症相关成纤维细胞浸润。预先存在的瘤内 T 细胞的克隆型动态是反应性患者的标志。这些发现为新辅助抗 PD-L1 单药治疗作为可切除 ESCC 患者的治疗策略提供了合理依据。

更新日期:2023-07-25
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