PD-1/PD-L1抑制剂治疗小细胞肺癌疗效及预后的真实世界研究  

Effect and prognosis of PD-1/PD-L1 inhibitors in treatment of small cell lung cancer:A realworld study

作　　者：周宇欣 邵佳康 张正 张砾 贾谷和 焦顺昌[2] ZHOU Yuxin;SHAO Jiakang;ZHANG Zheng;ZHANG Li;JIA Guhe;JIAO Shunchang(Chinese PLA Medical School,Beijing 100853,China;Department of Oncology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Medical College of Nankai University,Tianjin 300071,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第一医学中心肿瘤内科,北京100853 [3]南开大学医学院,天津300071

出　　处：《解放军医学院学报》2024年第2期105-111,共7页Academic Journal of Chinese PLA Medical School

基　　金：国家十三五重大专项课题项目(2018ZX09201013)。

摘　　要：背景以PD-1/PD-L1抑制剂为主的免疫治疗在小细胞肺癌(small cell lung cancer,SCLC)一线治疗中取得重大突破,但在复杂的真实世界背景下,其疗效和安全性需要进一步验证。目的分析SCLC患者接受PD-1/PD-L1抑制剂治疗的有效性和安全性,并分析其预后影响因素。方法收集解放军总医院第一医学中心2013年8月—2022年6月收治的经PD-1/PD-L1抑制剂治疗的SCLC患者的临床资料,分析其疗效和免疫相关不良反应(immune-related adverse events,irAEs)发生率,使用Kaplan-Meier生存曲线和Log-rank检验评估不同因素对患者生存的影响,使用单因素和多因素Cox回归分析不同因素与预后的关系。结果共250例患者纳入研究,其中男性213例(85.2%),女性37例(14.8%),中位年龄60.5岁。其中局限期(limited stage-SCLC,LS-SCLC)62例(24.8%),广泛期(extensive stage-SCLC,ES-SCLC)188例(75.2%)。中位无进展生存期(progression-free survival,PFS)为7.6(95%CI:6.2~9.0)个月,中位总生存期(overall survival,OS)为18.2(95%CI:14.7~21.7)个月。免疫治疗再挑战组(rechallenge of immunotherapy beyond progression,RIBP)相比进展后停止免疫治疗组(discontinuation of immunotherapy beyond progression,DIBP)OS显著延长(OS:10.2个月vs 5.1个月,P=0.004)。出现任何级别irAEs患者的OS优于未出现irAEs患者(OS:29.2个月vs 16.1个月,P=0.003)。多因素Cox分析结果提示,肝转移(HR=2.427,95%CI:1.648~3.573,P<0.001)、Ki67指数(HR=1.491,95%CI:1.009~2.203,P=0.045)和治疗线数(HR=1.601,95%CI:1.111~2.306,P=0.011)是独立影响PFS的预后因素,肝转移(HR=3.325,95%CI:2.191~5.046,P<0.001)和疾病分期(HR=2.092,95%CI:1.163~3.761,P=0.014)是OS的独立预后因素。3级及以上一般不良事件发生率低于24%,3级及以上免疫相关不良事件发生率低于11%,未发生导致死亡的不良事件。结论以PD-1/PD-L1抑制剂为主的免疫治疗对SCLC患者的疗效可靠,安全性可耐受。肝转移和疾病分期与OS独立关联。免疫治疗进展�Background Immunotherapy based on PD-1/PD-L1 inhibitors has made a major breakthrough in the first-line treatment of small cell lung cancer(SCLC),but its efficacy and safety need to be further verified in a complex real-world context.Objective To analyze the efficacy and safety in SCLC patients with PD-1/PD-L1 inhibitor treatment and its prognostic factors.Methods Clinical data about SCLC patients treated with PD-1/PD-L1 inhibitors in the First Medical Center of Chinese PLA General Hospital from August 2013 to June 2022 were collected.The efficacy and the incidence of immune-related adverse events(irAEs)were analyzed.Kaplan-Meier survival curve was used to analyze the effects of different factors on the survival of patients.Univariate and multivariate Cox regression analyses were used to analyze the relationship between different factors and prognosis.Results A total of 250 patients were included in the study,including 213 males(85.2%)and 37 females(14.8%),with a median age of 60.5 years.There were 62 cases(24.8%)of limited stage-SCLC(LS-SCLC)and 188 cases(75.2%)of extensive stage-SCLC(ES-SCLC).The median progression-free survival(PFS)was 7.6 months(95%CI:6.2-9.0),and the median overall survival(OS)was 18.2 months(95%CI:14.7-21.7).The OS of the re-challenge of immunotherapy beyond progression(RIBP)group was significantly longer than that of the discontinuation of immunotherapy beyond progression(DIBP)group(OS:10.2 months vs 5.1 months,P=0.004).The OS of patients with irAEs of any grade was better than that of patients without irAEs(OS:29.2 months vs 16.1 months,P=0.003).Multivariate Cox analysis showed that liver metastasis(HR=2.427,95%CI:1.648-3.573,P<0.001),Ki67 index(HR=1.491,95%CI:1.009-2.203,P=0.045)and treatment lines(HR=1.601,95%CI:1.111-2.306,P=0.011)were independent prognostic factors for PFS.Liver metastasis(HR=3.325,95%CI:2.191-5.046,P<0.001)and disease stage(HR=2.092,95%CI:1.163-3.761,P=0.014)were independent prognostic factors for OS.The incidence of grade 3 and above general adverse events was less

关 键 词：小细胞肺癌 PD-1/PD-L1抑制剂 免疫治疗 无进展生存期 总生存期 安全性 

分 类 号：R734.2[医药卫生—肿瘤]