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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (7): 74-82.doi: 10.6040/j.issn.1671-7554.0.2022.0238

• 临床医学 • 上一篇    下一篇

晚期驱动基因阴性、PD-L1表达阴性非鳞非小细胞肺癌一线治疗方案的网状Meta分析

秦静,杨飞,陈谦,夏涵岱,刘延国,王秀问   

  1. 山东大学齐鲁医院化疗科, 山东 济南 250012
  • 发布日期:2022-07-27
  • 通讯作者: 王秀问. E-mail:xiuwenwang12@ sdu.edu.cn 刘延国. E-mail:liuyanguo@sdu.edu.cn
  • 基金资助:
    国家自然科学基金面上项目(81874044);山东省自然科学基金面上项目(ZR2020MH236,ZR2019MH050);北京市希思科临床肿瘤学研究基金(Y-QL2019-0376)

A network meta-analysis of first-line treatment options for patients with advanced driver-gene wild-type and PD-L1 negative non-squamous non-small cell lung cancer

QIN Jing, YANG Fei, CHEN Qian, XIA Handai, LIU Yanguo, WANG Xiuwen   

  1. Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2022-07-27

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摘要： 目的 对晚期驱动基因阴性、程序性死亡配体1(PD-L1)表达阴性非鳞非小细胞肺癌(NSCLC)一线治疗方案疗效和安全性进行网状Meta分析。 方法 检索PubMed、Cochrane Library、Embase数据库及ClinicalTrials.gov网站有关晚期驱动基因阴性非鳞NSCLC一线治疗研究,纳入包括化疗、免疫检查点抑制剂(ICIs)、抗血管生成药物及其联合治疗的随机对照试验(RCT),使用StataMP 16. 0及R 4.1.0软件进行网状Meta分析。 结果 共纳入10个RCT、5731例非鳞NSCLC患者,涉及10种治疗方案。各治疗方案总生存期(OS)和无进展生存期(PFS)差异无统计学意义(P均>0.05)。OS概率排序居第1位的是帕博利珠单抗联合化疗,PFS概率排序居第1位的是纳武利尤单抗联合贝伐珠单抗及化疗。在有效率方面,阿替利珠单抗联合化疗、帕博利珠单抗联合化疗的客观缓解率(ORR)高于化疗(OR=1.66,95%CI:1.07~2.59;OR=2.68,95%CI:1.40~5.11)。在所有级别不良反应率方面,卡瑞利珠单抗联合化疗的不良反应率高于化疗及信迪利单抗联合化疗(OR=1.05,95%CI:1.01~1.08;OR=1.05,95%CI:1.01~1.09)。在≥3级不良反应率方面,各治疗方案差异无统计学意义(P均>0.05)。 结论 对于PD-L1表达阴性的晚期驱动基因阴性非鳞NSCLC患者,现有的一线治疗方案在生存获益上未见明显差异。免疫联合化疗有效率更高、但不良反应也更为显著,需根据患者个体状况选择合理的治疗方案。

关键词: 非小细胞肺癌, 网状Meta分析, 程序性死亡配体1, 化疗, 抗血管生成治疗, 免疫治疗

Abstract: Objective A network meta-analysis was performed to compare the efficacy and safety of first-line treatment regimens of advanced driver-gene wild-type and programmed death-ligand 1(PD-L1)negative non-squamous non-small cell lung cancer(NSCLC). Methods First-line treatment trials of advanced driver-gene wild-type non-squamous NSCLC were searched in PubMed, Cochrane Library, Embase database and ClinicalTrials.gov website. Randomized controlled trials(RCTs)comparing first-line treatment regimens including chemotherapy, immune checkpoint inhibitors(ICIs), antiangiogenic therapy and their combinations were included. StataMP 16.0 and R 4.1.0 were used for data analysis. Results A total of 10 RCTs were included, involving 5,731 patients and 10 treatment regimens. There was no statistically significant difference in overall survival(OS)and progression-free survival(PFS)among the treatment regimens(P>0.05). The regimen of pembrolizumab + chemotherapy had the longest OS, and the regimen of nivolumab+bevacizumab+chemotherapy had the longest PFS. The objective response rates(ORR)of atezolizumab+ chemotherapy and pembrolizumab+chemotherapy were higher than that of chemotherapy(OR=1.66, 95%CI: 1.07-2.59; OR=2.68, 95%CI: 1.40-5.11). In terms of allgrade adverse events(AEs), camrelizumab + chemotherapy was higher(AEs)than chemotherapy and sintilimab + chemotherapy(OR=1.05, 95%CI: 1.01-1.08; OR=1.05, 95%CI: 1.01-1.09). In terms of ≥3 grade AEs, there was no statistically significant difference among the treatment regimens(P>0.05). Conclusion For patients with advanced driver-gene wild-type PD-L1 negative non-squamous NSCLC, there was no significant difference in survival benefits among the existing first-line treatment regimens. The combination of immunotherapy and chemotherapy was more effective, but the adverse events were also more significant. A reasonable treatment regimen should be selected according to the individual conditions.

Key words: Non-small cell lung cancer, Network meta-analysis, Programmed death-ligand 1, Chemotherapy, Antiangiogenic therapy, Immunotherapy

中图分类号: 

  • R734.2
[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021 [J]. CA Cancer J Clin, 2021, 71(1): 7-33.
[2] 黄岩, 张力. 2020 CSCO非小细胞肺癌诊疗指南更新要点解读[J]. 临床内科杂志, 2020, 37(8): 603-605.
[3] 王建丽, 王筱静, 孙玉莲, 等. 吉非替尼联合化疗治疗50例晚期非小细胞肺癌患者的疗效[J]. 山东大学学报(医学版), 2019, 57(11): 20-26. WANG Jianli, WANG Xiaojing, SUN Yulian, et al. Clinical effect of gefitinib combined with chemotherapy on patients with advanced non-small cell lung cancer [J]. Journal of Shandong University(Health Sciences), 2019, 57(11): 20-26.
[4] Chen R, Manochakian R, James L, et al. Emerging therapeutic agents for advanced non-small cell lung cancer [J]. J Hematol Oncol, 2020, 13(1): 58. doi: 10.1186/s13045-020-00881-7.
[5] Herbst R, Jassem J, Abogunrin S, et al. A network meta-analysis of cancer immunotherapies versus chemotherapy for first-line treatment of patients with non-small cell lung cancer and high programmed death-ligand 1 expression [J]. Front Oncol, 2021, 11: 676732. doi: 10.3389/fonc.2021.676732. eCollection 2021.
[6] Ettinger DS, Wood DE, Aisner DL, et al. NCCN guidelines insights: non-small cell lung cancer, version 2.2021 [J]. J Natl Compr Canc Netw, 2021, 19(3): 254-266.
[7] Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer(CameL): a randomised, open-label, multicentre, phase 3 trial [J]. Lancet Resp Med, 2021, 9(3): 305-314.
[8] Yang Y, Wang Z, Fang J, et al. Efficacy and safety of sintilimab plus pemetrexed and platinum as first-line treatment for locally advanced or metastatic nonsquamous NSCLC: a randomized, double-blind, phase 3 study(Oncology pRogram by InnovENT anti-PD-1-11)[J]. J Thorac Oncol, 2020, 15(10): 1636-1646.
[9] West H, Mccleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer(IMpower130): a multicentre, randomised, open-label, phase 3 trial [J]. Lancet Oncol, 2019, 20(7): 924-937.
[10] Nishio M, Barlesi F, West H, et al. Atezolizumab plus chemotherapy for first-line treatment of nonsquamous NSCLC: results from the randomized phase 3 IMpower132 Trial [J]. J Thorac Oncol, 2021, 16(4): 653-664.
[11] Socinski MA, Nishio M, Jotte RM, et al. IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous NSCLC [J]. J Thorac Oncol, 2021, 16(11): 1909-1924.
[12] Borghaei H, Langer CJ, Gadgeel S, et al. 24-month overall survival from KEYNOTE-021 cohort G: pemetrexed and carboplatin with or without pembrolizumab as first-line therapy for-advanced nonsquamous non-small cell lung cancer [J]. J Thorac Oncol, 2019, 14(1): 124-129.
[13] Garon EB, Aerts J, Kim JS, et al. Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: a post hoc analysis of KEYNOTE-189 [J]. Lung Cancer, 2021, 155: 53-60. doi: 10.1016/j.lungcan.2021.02.021.
[14] Hellmann MD, Paz-ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer [J]. New Engl J Med, 2019, 381(21): 2020-2031.
[15] Lu S, Wang J, Yu Y, et al. Tislelizumab plus chemotherapy as first-line treatment for locally advanced or metastatic nonsquamous NSCLC(RATIONALE 304): a randomized phase 3 trial [J]. J Thorac Oncol, 2021, 16(9): 1512-1522.
[16] Sugawara S, Lee JS, Kang JH, et al. Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer [J]. Ann Oncol, 2021, 32(9): 1137-1147.
[17] Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review [J]. JAMA, 2019, 322(8): 764-774.
[18] Gubens MA, Davies M. NCCN guidelines updates: new immunotherapy strategies for improving outcomes in non-small cell lung cancer [J]. J Natl Compr Canc Netw, 2019, 17(5.5): 574-578.
[19] Shi Y, Duan J, Guan Q, et al. Effectivity and safety of PD-1/PD-L1 inhibitors for different level of PD-L1-positive, advanced NSCLC: a meta-analysis of 4939 patients from randomized controlled trials [J]. Int Immunopharmacol, 2020, 84: 106452. doi:10.1016/j.intimp.2020.106452.
[20] Liu J, Li C, Seery S, et al. Identifying optimal first-line interventions for advanced non-small cell lung carcinoma according to PD-L1 expression: a systematic review and network meta-analysis [J]. Oncoimmunology, 2020, 9(1): 1746112. doi: 10.1080/2162402X.2020.1746112.
[21] 秦叔逵, 马军, 李进, 等. 卡瑞利珠单抗致反应性皮肤毛细血管增生症临床诊治专家共识[J]. 临床肿瘤学杂志, 2020, 25(9): 840-848. QIN Shukui, MA Jun, LI Jin, et al. Expert consensus on the clinical diagnosis and treatment of camrelizumab induced reactive cutaneous capillary endothelial proliferation [J]. Chinese Clinical Oncology, 2020, 25(9): 840-848.
[22] Gadgeel S, Rodríguez-abreu D, Speranza G, et al. Updated analysis from KEYNOTE-189: pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer [J]. J Clin Oncol, 2020, 38(14): 1505-1517.
[23] Garcia J, Hurwitz HI, Sandler AB, et al. Bevacizumab(Avastin®)in cancer treatment: a review of 15 years of clinical experience and future outlook [J]. Cancer Treat Rev, 2020, 86: 102017. doi: 10.1016/j.ctrv.2020.102017.
[24] Shroff GS, Strange CD, Altan M, et al. Post-immunotherapy imaging in lung cancer [J]. Clin Radiol, 2022, 77(1): 44-57.
[25] Hellmann MD, Paz-ares L, Bernabe CR, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer [J]. N Engl J Med, 2019, 381(21): 2020-2031.
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