PD-1/PD-L1抑制剂联合抗血管生成药物治疗晚期非小细胞肺癌的临床观察  

Clinical observation of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy in the treatment of advanced non-small cell lung cancer

作　　者：邱鲁鹏 赵晓[2] 刘茗露 杜思成 焦顺昌[2] QIU Lupeng;ZHAO Xiao;LIU Minglu;DU Sicheng;JIAO Shunchang(Department of Medical Oncology, the First Medical Centre, Chinese People's Liberation Army General Hospital, Beijing 100853, China)

机构地区：[1]解放军总医院研究生院,北京100853 [2]解放军总医院第一医学中心肿瘤内科,北京100853

出　　处：《临床肿瘤学杂志》2022年第5期411-418,共8页Chinese Clinical Oncology

摘　　要：目的 探讨程序性死亡受体-1(PD-1)和程序性死亡受体-配体1(PD-L1)抑制剂联合抗血管生成药物治疗晚期非小细胞肺癌(NSCLC)的临床疗效和不良反应,并探索潜在的预后相关因素。方法 回顾性分析2015年1月至2019年12月于我院接受PD-1/PD-L1抑制剂联合抗血管生成药物治疗的49例晚期NSCLC患者,观察患者的临床疗效、不良反应及生存情况,并探讨治疗前外周血粒淋比(NLR)和乳酸脱氢酶(LDH)与生存预后的相关性。结果 共纳入49例晚期NSCLC患者,其中完全缓解(CR)0例,部分缓解(PR)14例,疾病稳定(SD)22例,总体客观缓解率(ORR)为28.6%,疾病控制率(DCR)为73.5%。至随访截止时间,全组患者的中位无进展生存期(PFS)为5.7个月(95%CI:4.6~6.8个月),中位总生存期(OS)为12.9个月(95%CI:4.7~21.1个月)。多因素Cox回归分析结果显示,治疗前LDH水平是影响患者PFS(HR=3.020,95%CI:1.539~5.925,P=0.001)和OS(HR=2.403,95%CI:1.157~4.990,P=0.019)的独立预后因素。35例患者发生了药物相关不良反应,其中较常见的为疲劳、皮疹、恶心、腹泻、高血压等。3~4级不良反应的发生率为8.2%(4/49),分别为腹泻1例、肺炎1例、肝功能损伤1例及中性粒细胞减少1例。结论 PD-1/PD-L1抑制剂联合抗血管生成药物治疗晚期NSCLC显示了良好的临床疗效,且不良反应相对可控。治疗前外周血LDH水平是影响患者PFS和OS的独立预后因素,有助于筛选能从该治疗方案中获益的潜在人群。Objective To analyze the clinical efficacy and adverse events of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy in the treatment of advanced non-small cell lung cancer(NSCLC),and explore the potential prognostic factors.Methods Our study retrospectively analyzed 49 patients with advanced NSCLC who received PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy in our hospital from January 2015 to December 2019.The clinical efficacy,adverse events and the survival of the enrolled patients were observed,and the correlation between prognosis and peripheral blood markers such as neutrophil-lymphocyte ratio(NLR)and lactate dehydrogenase(LDH)was analyzed.Results A total of 49 patients were enrolled in our study,including 0 complete response(CR),14 partial response(PR),and 22 stable disease(SD).The overall objective response rate(ORR)was 28.6%and the disease control rate(DCR)was 73.5%.At the end of follow-up,the median progression-free survival(PFS)was 5.7 months(95%CI:4.6-6.8),and the median overall survival(OS)was 12.9 months(95%CI:4.7-21.1).Multivariate analysis showed that LDH was an independent prognostic factor that affects PFS(HR=3.020,95%CI:1.539-5.925,P=0.001)and OS(HR=2.403,95%CI:1.157-4.990,P=0.019).Drug-related adverse events occurred in 35 patients,including fatigue,rash,nausea,diarrhea,hypertension and so on.The incidence of grade 3-4 adverse events was 8.2%(4/49),including 1 case of diarrhea,1 case of pneumonia,1 case of liver damage,and 1 case of neutropenia.Conclusion Our study shows that the combination of PD-1/PD-L1 inhibitors and anti-angiogenic therapy can bring survival benefits for patients with advanced NSCLC,and the adverse events are relatively controllable.The level of serum LDH before treatment can be used as an independent prognostic factor to predict PFS and OS,which is helpful to screen the potential patients who can benefit from this treatment regimen.

关 键 词：非小细胞肺癌 PD-1/PD-L1抑制剂 抗血管生成治疗 乳酸脱氢酶 总生存期 

分 类 号：R734.2[医药卫生—肿瘤]