2024 年第 12 期 第 19 卷

程序性细胞死亡蛋白1抑制剂联合化疗对老年晚期食管鳞状细胞癌患者的有效性和安全性观察

The efficacy and safety of programmed cell death protein 1 inhibitor combined with chemotherapy in elderly patients with advanced esophageal squamous cell carcinoma

作者：别志欣1郭润碛1李彬1王承恩1徐圣1李元明1李晓光1李琳2

英文作者：Bie Zhixin1 Guo Runqi1 Li Bin1 Wang Cheng′en1 Xu Sheng1 Li Yuanming1 Li Xiaoguang1 Li Lin2

单位：1北京医院肿瘤微创治疗中心国家老年医学中心中国医学科学院老年医学研究院，北京100730；2北京医院肿瘤科国家老年医学中心中国医学科学院老年医学研究院，北京100730

英文单位：1Cancer Minimally Invasive Treatment Center Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing 100730 China; 2Department of Oncology Beijing Hospital Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing 100730 China

关键词：食管鳞状细胞癌；程序性细胞死亡蛋白1抑制剂；化疗

英文关键词：Esophagealsquamouscellcarcinoma;Programmedcelldeathreceptor1inhibitor;Chemotherapy

• 摘要：

• 目的 探讨程序性细胞死亡蛋白1（PD-1）抑制剂联合化疗对老年晚期食管鳞状细胞癌患者的有效性和安全性。方法 本研究为回顾性队列研究，连续纳入2019年10月至2022年12月在北京医院诊治的老年不可切除局部晚期或转移性食管鳞状细胞癌患者95例。按照是否应用PD-1抑制剂分为PD-1抑制剂组（30例）和对照组（65例）。2组患者均给予紫杉醇+顺铂方案化疗，此外PD-1抑制剂组还给予PD-1抑制剂。紫杉醇+顺铂方案化疗和PD-1抑制剂均为每3周1个治疗周期。治疗直至疾病进展或者患者不能耐受或者患者死亡。随访截止至2023年12月31日，比较2组的总生存期、无进展生存期和客观缓解率等，应用多因素Cox回归分析方法评估影响总生存期的重要因素。结果 与对照组相比，PD-1抑制剂组患者的年龄相对较大，但差异无统计学意义（P>0.05）。随访期间，死亡65例，PD-1抑制剂组和对照组分别有16例（53.3%）和49例（75.4%）。PD-1抑制剂组的总生存期［15.1（12.4,18.9）个月比11.3（9.2,15.7）个月，P=0.002］、无进展生存期［6.6（5.0,7.4）个月比5.0（3.8,6.6）个月，P=0.004］长于对照组，客观缓解率高于对照组［56.7%（17/30）比40.0%（26/65）， χ2=4.196，P=0.041］。PD-1抑制剂组和对照组患者≥3级不良反应发生率比较差异无统计学意义［56.7%（17/30）比50.8%（33/65）， χ2=0.793，P=0.261］。多因素Cox回归分析结果显示，体重指数、美国东部肿瘤协作组评分、入组时为远处转移病变、程序性细胞死亡受体配体1联合阳性评分≥1分和PD-1抑制剂治疗是影响总生存期的重要因素（风险比=0.893、0.779、1.730、0.693、0.772，均P<0.05）。结论 PD-1抑制剂联合化疗对老年晚期食管鳞状细胞癌患者具有良好的有效性和安全性。

• Objective To investigate the efficacy and safety of programmed cell death protein 1 （PD-1） inhibitor combined with chemotherapy in elderly patients with advanced esophageal squamous cell carcinoma. Methods This study was a retrospective cohort study. A total of 95 elderly patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma diagnosed and treated in Beijing Hospital from October 2019 to December 2022 were consecutively enrolled. The patients were divided into PD-1 inhibitor group (30 cases) and control group (65 cases) according to whether PD-1 inhibitors were used. Both groups were given paclitaxel and cisplatin chemotherapy, and PD-1 inhibitor group was also given PD-1 inhibitor. Paclitaxel and cisplatin chemotherapy and PD-1 inhibitor were given every 3 weeks. The patients were treated until disease progression or intolerance or death. The follow-up ended on December 31, 2023. The overall survival, progression-free survival and objective response rate of the two groups were compared, and the important factors affecting overall survival were evaluated by multivariate Cox regression analysis. Results Patients in the PD-1 inhibitor group were relatively older than those in the control group, but the difference was not statistically significant (P>0.05). During the follow-up period, 65 patients died, including 16 cases (53.3%) in the PD-1 inhibitor group and 49 cases (75.4%) in the control group. The overall survival ［15.1(12.4,18.9)months vs 11.3(9.2,15.7)months, P=0.002］ and progression-free survival ［6.6(5.0,7.4)months vs 5.0(3.8,6.6)months, P=0.004］ of the PD-1 inhibitor group were longer than those of the control group, and the objective response rate was higher than that of the control group ［56.7%(17/30) vs 40.0%(26/65), χ2=4.196, P=0.041］. There was no significant difference in the incidence of grade ≥3 adverse reactions between the PD-1 inhibitor group and the control group ［56.7%（17/30） vs 50.8%（33/65）, χ2=0.793, P=0.261］. Multivariate Cox regression analysis showed that body mass index, Eastern Cooperative Oncology Group score, distant metastasis at enrollment, programmed cell death ligand 1 combined positive score ≥1 and PD-1 inhibitor treatment were important factors affecting overall survival (hazard ratio=0.893, 0.779, 1.730, 0.693, 0.772; all P<0.05). Conclusion PD-1 inhibitor combined with chemotherapy has good efficacy and safety in elderly patients with advanced esophageal squamous cell carcinoma.