PD-1单抗联合化疗用于初始不能手术的局部晚期转移性老年食管鳞癌病人的转化治疗研究

doi:10.3969/j.issn.1003-9198.2025.12.013

摘要/Abstract

摘要： 目的评估程序性死亡受体1(PD-1)单抗联合顺铂和5-氟尿嘧啶治疗初始不能手术的老年晚期食管鳞状细胞癌(ESCC)病人的疗效和安全性及手术转化率。方法研究纳入26例老年病人和21例非老年病人,均接受3个周期的PD-1单抗、顺铂和5-氟尿嘧啶的诱导治疗。记录程序性死亡配体1(PD-L1)的表达和肿瘤突变负荷(TMB),主要观察指标为3级及以上不良事件发生率、主要病理缓解(MPR)率和病理完全缓解(pCR)率,次要观察指标包括手术转化率、R0切除率、无进展生存期(PFS)、总生存期(OS)。结果老年组和非老年组3级及以上不良事件发生率分别为15.4%和14.3%(P=0.916),MPR率分别为46.2%和33.3%(P=0.373),pCR率分别为42.3%和23.8%(P=0.237)。次要观察指标:老年组和非老年组的手术转化率分别为56.5%和50.0%(P=0.669)。R0切除率方面,老年组为100%,非老年组为90.0%(P=0.244)。生存分析显示,老年组和非老年组的中位PFS分别为未达到和16个月(P=0.041);中位OS分别为36个月和22个月(P=0.029)。在老年组中,成功接受手术的病人较未手术病人具有更长的PFS(24个月比9个月,P=0.01)和OS(未达到比16个月,P=0.007)。此外,TMB≥10个突变/Mb的病人在手术组中表现出更优的PFS(未达到比20个月,P=0.049)。PD-L1表达状态对生存期无显著影响(P=0.172)。结论 PD-1单抗联合化疗对老年ESCC有效,不良事件可耐受。相比于非老年病人,老年病人可获得显著的生存获益。PD-1单抗联合化疗用于初始不能手术的老年ESCC病人的手术转化治疗是一种有前景的治疗方案。

关键词: 食管鳞状细胞癌, 老年人, 免疫联合化疗, 诱导治疗, PD-1单抗

Abstract: Objective To evaluate the efficacy and safety of programmed death-1 (PD-1) monoclonal antibody combined with cisplatin and 5-fluorouracil in elderly patients with initially unresectable advanced esophageal squamous cell carcinoma (ESCC), as well as the surgical conversion rate. Methods The study enrolled 26 elderly patients and 21 non-elderly patients, all of whom received three cycles of induction therapy with PD-1 monoclonal antibody, cisplatin, and 5-fluorouracil. PD-L1 expression and tumor mutational burden (TMB) were recorded. Primary endpoints were the incidence of grade 3 or higher adverse events, major pathological response (MPR) rate, and pathological complete response (pCR) rate. Secondary endpoints included surgical conversion rate, R0 resection rate, progression-free survival (PFS), and overall survival (OS). Results The incidence rate of grade 3 or higher adverse events was 15.4% in the elderly group and 14.3% in the non-elderly group (P=0.916). The MPR rate was 46.2% and 33.3% (P=0.373), and the pCR rate was 42.3% and 23.8% (P=0.237) in the elderly group and the non-elderly group, respectively. For secondary endpoints, the surgical conversion rate was 56.5% in the elderly group and 50.0% in the non-elderly group (P=0.669); The R0 resection rate was 100% in the elderly group and 90.0% in the non-elderly group (P= 0.244). Survival analysis showed that the median PFS was not reached in the elderly group and was 16 months in the non-elderly group (P=0.041), and the median OS was 36 months and 22 months, respectively (P=0.029). In the elderly group, patients who successfully underwent surgery had significantly longer PFS (24 months vs 9 months, P=0.01) and OS (not reached vs 16 months, P=0.007) compared to those who did not undergo surgery. Additionally, patients with TMB ≥10 mutations/Mb in the surgical group showed better PFS (not reached vs 20 months, P=0.049). PD-L1 expression status had no significant impact on survival (P=0.172). Conclusions PD-1 monoclonal antibody combined with chemotherapy is effective and tolerable in elderly patients with ESCC, associated with a superior survival benefit compared to non-elderly patients. PD-1 monoclonal antibody combined with chemotherapy is a promising treatment strategy for surgical conversion therapy in elderly patients with initially unresectable advanced ESCC.

Key words: esophageal squamous cell carcinoma, aged, immunotherapy combined with chemotherapy, induction conversion therapy, programmed death-ligand 1 antibody

中图分类号:

R 735.1

沈海瑞, 徐同鹏. PD-1单抗联合化疗用于初始不能手术的局部晚期转移性老年食管鳞癌病人的转化治疗研究[J]. 实用老年医学, 2025, 39(12): 1253-1258.

SHEN Hairui, XU Tongpeng. Conversion therapy for elderly patients with unresectable local advanced esophageal squamous cell carcinoma by PD-1 antibody plus chemotherapy[J]. Practical Geriatrics, 2025, 39(12): 1253-1258.

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