阿得贝利单抗新辅助治疗用于局部晚期可切除食管鳞状细胞癌：1b期试验

2023-08-10 09:56

预先存在的肿瘤内T细胞的肿瘤克隆型动力学是有病理学反应患者的生物学标志。这些发现为新辅助抗PD-L1单药治疗可切除ESCC患者提供了合理的治疗策略。

SCI

9 August 2023

Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial

(Nature Medicine, IF: 82.9)

Jun Yin, Jingnan Yuan, Yunjin Li, Yong Fang, Ruoxi Wang, Heng Jiao, Han Tang, Shaoyuan Zhang, Siyun Lin, Feng Su, Jianmin Gu, Tian Jiang, Dong Lin, Zhiliang Huang, Chaoxiang Du, Kui Wu , Lijie Tan & Qing Zhou

CORRESPONDENCE TO: wukui@genomics.cn, tan.lijie@zs-hospital.sh.cn, zhouqing2@genomics.cn

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. ClinicalTrials.gov identifier: NCT04215471.

在局部晚期食管鳞状细胞癌（ESCC）中，新辅助免疫疗法的总生存率（OS）获益仍然难以捉摸。在此，我们报道了阿得贝利单抗新辅助PD-L1阻断可切除ESCC的1b期试验结果。患者接受两次新辅助阿得贝利单抗治疗，然后进行手术。试验主要终点是安全性和可行性；次要终点包括病理完全反应（pCR）和OS。我们的数据显示，已经达到了安全性和可行性的主要终点。常见的治疗相关不良事件为厌食症（32%）和疲劳症（16%），无3级或以上不良事件。在参与试验的30名患者中，25名患者在没有延迟手术时间的情况下成功完成病灶切除手术，24%的患者有主要病理学反应，其中pCR率为8%。这些患者中的2年OS率为92%。有病理学反应的患者具有免疫富集的肿瘤微环境表型，而无病理学反应的患者在基线状态时癌症相关成纤维细胞的浸润程度更广。预先存在的肿瘤内T细胞的肿瘤克隆型动力学是有病理学反应患者的生物学标志。这些发现为新辅助抗PD-L1单药治疗可切除ESCC患者提供了合理的治疗策略。