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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (4): 432-439.doi: 10.3969/j.issn.1674-5671.2025.04.06

• 论著 • 上一篇    下一篇

一线免疫治疗失败的晚期食管鳞癌患者行免疫联合化疗与二线化疗的疗效和安全性比较

  

  1. 首都医科大学附属北京同仁医院血液内科；首都医科大学附属复兴医院呼吸内科
  • 出版日期:2025-08-25 发布日期:2025-09-11
  • 基金资助:
    家自然科学基金青年基金项目（82102954） 

A comparative analysis of efficacy and safety of immune checkpoint inhibitor in combination with chemotherapy versus second⁃line chemotherapy in patients with advanced esophageal squamous cell carcinoma following first⁃line immunotherapy

  • Online:2025-08-25 Published:2025-09-11

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摘要： 目的 评估免疫检查点抑制剂（immune checkpoint inhibitor, ICI）联合化疗与二线化疗在一线免疫治疗失败后进展或转移性食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）患者中的疗效和安全性。方法 纳入2019年9月至2023年12月在武汉大学人民医院肿瘤中心接受治疗的晚期ESCC患者。将一线免疫治疗进展后仅接受二线单纯化疗的患者作为单纯化疗组，使用ICI联合化疗的患者归为ICI联合化疗组。比较两组患者的总生存期（overall survival,OS）、无进展生存期（progression⁃free survival，PFS）、客观缓解率（objective response rate，ORR）、疾病控制率（disease control rate，DCR）和安全性。结果 共筛选出112例符合标准的患者，其中单纯化疗组31例，ICI联合化疗组81例。生存分析显示，ICI联合化疗组的OS显著长于单纯化疗组（10.8个月 vs 6.9个月；HR=0.56, 95%CI:0.34~0.89；P=0.013），DCR也更高（80.2% vs 58.1%；OR=0.35，95%CI：0.15~0.81；P=0.016）。但PFS未见显著延长（5.0个月 vs 3.7个月；HR=0.79, 95%CI:0.50~1.23；P=0.293），ORR也无明显差异（33.3% vs 16.1%；OR=0.38，95%CI：0.15~1.14；P=0.071）。亚组分析表明，肿瘤位于食管中段、Ⅲ~Ⅳ期手术分期、存在远处转移或PD⁃L1 阳性评分（combined positive score，CPS）≥10的男性患者，无论一线PFS持续时间长短，均能从化疗联合ICI治疗中获益。单纯化疗组和ICI联合化疗组的任何级别治疗相关不良事件（treatment⁃related adverse events，TRAEs）总发生率分别为93.5%和98.8%（P=0.126），其中≥3级TRAEs发生率分别为29.0%和34.6%（P=0.577）。所有3级及以上TRAEs均可通过对症治疗缓解。结论 与单纯化疗相比，一线免疫治疗失败的晚期ESCC患者，化疗联合ICI治疗显示出显著的生存获益和可控的安全性。

关键词: 食管鳞状细胞癌, 免疫检查点抑制剂, 化疗, 二线治疗, 疗效, 安全性

Abstract: Objective To evaluate the efficacy and safety of combining immune checkpoint inhibitor (ICI) with chemotherapy， as opposed to administering second⁃line chemotherapy alone， in patients with progressive or metastatic esophageal squamous cell carcinoma (ESCC) who have experienced failure of first⁃line immunotherapy. Methods The study included patients with advanced ESCC who were treated at the Department of Oncology， Renmin Hospital of Wuhan University， from September 2019 to December 2023. Patients who received only second⁃line chemotherapy following progression on first⁃line immunotherapy were designated as the chemotherapy⁃alone group， whereas those who received a combination of ICI and chemotherapy were classified as the ICI combined with chemotherapy group. The study compared overall survival (OS)， progression⁃free survival (PFS)， objective response rate (ORR)， disease control rate (DCR)， and safety outcomes between the two groups. Results A total of 112 eligible patients were screened， comprising 31 individuals in the chemotherapy⁃ alone group and 81 in the ICI combined with chemotherapy group. Survival analysis demonstrated that the ICI combined with chemotherapy group indicated a significantly longer OS compared to the chemotherapy⁃alone group (10.8 months vs 6.9 months; HR=0.56， 95%CI: 0.35-0.89; P=0.013) and a higher DCR (80.2% vs 58.1%; OR=0.35， 95%CI: 0.15-0.81; P=0.016). However， PFS was not significantly extended (5.0 months vs 3.7 months; HR=0.79， 95%CI : 0.50-1.23; P=0.293)， nor was the ORR (33.3% vs 16.1%; OR=0.38， 95%CI: 0.15-1.14; P=0.071). Subgroup analysis revealed that male patients with primary tumor located in the middle esophagus， stage Ⅲ-Ⅳ， distant metastasis， or PD⁃L1 combined positive score (CPS)  ≥10 derived greater benefit from the chemotherapy combined with ICI treatment， regardless of first⁃line PFS duration. The overall incidence of any grade treatment⁃related adverse events (TRAEs) was 93.5% in the chemotherapy⁃alone group and 98.8% in the ICI combined with chemotherapy group (P=0.126)， while the incidence of TRAEs of grade 3 or higher was 29.0% and 34.6% (P=0.577)， respectively; all grade 3 or higher TRAEs were resolved with symptomatic treatment.结论In patients with advanced ESCC who had previously failed first⁃line immunotherapy， the combination of chemotherapy and ICI treatment exhibited significant survival benefits and an acceptable safety profile compared to chemotherapy alone.

Key words: Esophageal squamous cell carcinoma, Immune checkpoint inhibitor, Chemotherapy, Second?line treatment, Efficacy, Safety

中图分类号: 

  • R735.1