免疫检查点抑制剂联合放疗或放化疗治疗肺癌疗效与安全性的Meta分析-现代医学

免疫检查点抑制剂联合放疗或放化疗治疗肺癌疗效与安全性的Meta分析

单位：1. 兰州大学第一临床医学院, 甘肃兰州 730000;
2. 甘肃省肿瘤医院肿瘤内科, 甘肃兰州 730000;
3. 兰州大学第一医院肿瘤内科, 甘肃兰州 730000;
4. 甘肃省胸部肿瘤临床医学研究中心, 甘肃兰州 730000

关键词：免疫检查点抑制剂放疗肺癌疗效安全性 Meta分析

分类号：R734.2

出版年·卷·期（页码）：2026·54·第六期（916-930）

摘要：

目的：系统评价免疫检查点抑制剂联合放疗或放化疗治疗肺癌的疗效和安全性。方法：计算机检索中国知网(CNKI)、中国生物医学文献数据库(SinoMed)、万方数据库(WF)、PubMed、Embase和Web of Science数据库，收集各数据库自建库起至2024年11月期间发表的相关文献。由2名研究员根据纳排标准独立开展文献筛选、资料提取，采用Cochrane协作网偏倚风险评估工具对所有纳入文献开展偏倚风险判定，运用Stata 18.0软件实施Meta分析。结果：共纳入18个随机对照试验(RCT)，包括2 789例患者。Meta分析结果显示：联合治疗组患者的客观缓解率(ORR)(RR=1.46，95%CI 1.20~1.76，P<0.05)、疾病控制率(DCR)(RR=1.14，95%CI 1.05~1.24，P<0.05)、无进展生存期(PFS)(HR=0.68，95%CI 0.56~0.82，P<0.05)和总生存期(OS)(HR=0.71，95%CI 0.61~0.82，P<0.05)均优于对照组。联合治疗组与对照组相比，两组≥3级不良事件发生率(RR=1.16，95%CI 0.76~1.77)差异无统计学意义(P>0.05)；但放射性肺炎、免疫相关性肺炎、乏力、甲状腺功能异常、皮肤损害及呼吸困难等不良事件发生率升高，差异有统计学意义(均P<0.05)。结论：免疫检查点抑制剂(ICIs)联合治疗可以明显改善肺癌患者的ORR、DCR、PFS、OS，并且联合治疗的整体不良反应可耐受。使用联合治疗方案时需要注意肺炎、乏力、甲状腺异常、皮肤损害、呼吸困难的发生，结合患者的个体情况做好不良反应的监测和预防。

Objective: To systematically assess the clinical efficacy and safety of immune checkpoint inhibitors combined with radiotherapy or chemoradiotherapy in the treatment of lung cancer.Methods: Literatures published from inception to November 2024 were electronically searched in the Sinomed, CNKI, Wanfang, PubMed, Embase and Web of Science databases. Two researchers independently completed literature screening and data extraction based on the inclusion and exclusion criteria. The risk of bias of all included studies was evaluated with the risk-of-bias tool from the Cochrane Collaboration, and Stata 18.0 software was adopted to perform the meta-analysis.Results: A total of 18 randomized controlled trials involving 2 789 patients were enrolled. Meta-analysis results showed that the combination therapy group had significantly higher objective response rates(RR=1.46, 95%CI 1.20-1.76, P < 0.05) and disease control rates(RR=1.14, 95%CI 1.05-1.24, P<0.05), as well as better progression-free survival(HR=0.68, 95%CI 0.56-0.82, P<0.05) and overall survival(HR=0.71, 95%CI 0.61-0.82, P<0.05) compared with the control group. Compared with the control group, there was no statistically significant difference in the incidence of grade ≥3 adverse events between the combination therapy group and the control group(RR=1.16, 95%CI 0.76-1.77, P>0.05); however, the incidences of radiation pneumonitis, immune-related pneumonitis, fatigue, thyroid dysfunction, skin damage, and dyspnea were significantly increased, with statistically significant differences(all P<0.05). Conclusion:Immune checkpoint inhibitors combined therapy can significantly improve the short-term efficacy and long-term survival of patients with lung cancer, with acceptable overall safety profile. Close clinical monitoring and targeted prevention of pneumonitis, fatigue, thyroid dysfunction, skin injury and dyspnea should be implemented based on individual patient conditions during clinical application.

参考文献：

[1] FILHO A M,LAVERSANNE M,FERLAY J,et al.The globocan 2022 cancer estimates:data sources,methods,and a snapshot of the cancer burden worldwide[J]. Int J Cancer,2025,156(7):1336-1346.
[2] 李彬,唐甜甜,胡欣.MAD2L1在肺癌中表达的研究进展[J]. 现代医学,2024,52(5):802-807.
[3] 朱晓丹,顾国民,沈艳丽,等.非小细胞肺癌中与免疫治疗应答相关的差异表达基因和KRAS突变分析[J]. 现代医学,2025,53(7):1069-1079.
[4] FELIP E,ALTORKI N,ZHOU C,et al.Overall survival with adjuvant atezolizumab after chemotherapy in resected stage Ⅱ-ⅢA non-small-cell lung cancer(IMpower010):a randomised,multicentre,open-label,phase Ⅲ trial[J]. Ann Oncol,2023,34(10):907-919.
[5] O'BRIEN M,PAZ-ARES L,MARREAUD S,et al.Pembrolizumab versus placebo as adjuvant therapy for completely resected stage ⅠB-ⅢA non-small-cell lung cancer(PEARLS/KEYNOTE-091):an interim analysis of a randomised,triple-blind,phase 3 trial[J]. Lancet Oncol,2022,23(10):1274-1286.
[6] RECK M,DZIADZIUSZKO R,SUGAWARA S,et al.Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase Ⅲ IMpower133 study and the Phase Ⅲ IMbrella A extension study[J]. Lung Cancer,2024,196:107924.
[7] GOLDMAN J W,DVORKIN M,CHEN Y,et al.Durvalumab,with or without tremelimumab,plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer(CASPIAN):updated results from a randomised,controlled,open-label,phase 3 trial[J]. Lancet Oncol,2021,22(1):51-65.
[8] CHENG Y,HAN L,WU L,et al.Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer:the ASTRUM-005 randomized clinical trial[J]. JAMA,2022,328(12):1223-1232.
[9] XUE H,CHEN Y,ZHOU Y.Radioimmunotherapy:a game-changer for advanced non-small cell lung cancer[J]. Front Immunol,2024,15:1522508.
[10] KIM J,LEE B J,MOON S,et al.Strategies to overcome hurdles in cancer immunotherapy[J]. Biomater Res,2024,28:80.
[11] WANG X,JING J.Cancer immunotherapy in combination with radiotherapy and/or chemotherapy:mechanisms and clinical therapy[J]. MedComm,2025,6(9):e70346.
[12] WEI J,LI W,ZHANG P,et al.Current trends in sensitizing immune checkpoint inhibitors for cancer treatment[J]. Mol Cancer,2024,23(1):279.
[13] ANTONIA S J,VILLEGAS A,DANIEL D,et al.Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer[J]. N Engl J Med,2017,377(20):1919-1929.
[14] 闵旭红,王尚虎,盛蕾,等.卡瑞利珠单抗联合同步放化疗治疗局部晚期非小细胞肺癌的临床分析[J]. 中华肿瘤防治杂志,2023,30(10):600-605.
[15] 侯士于.卡瑞利珠单抗联合调强适形放疗用于非小细胞肺癌患者的效果[J]. 中国民康医学,2024,36(4):56-58.
[16] 陆坤,沈辉,陈茜,等.卡瑞利珠单抗联合放化疗对局部晚期非小细胞肺癌患者生存预后的影响[J]. 医学研究与战创伤救治,2023,36(10):1066-1071.
[17] 国兵,吕玉凤.免疫制剂卡瑞利珠单抗联合同步放化疗治疗局部晚期NSCLC的临床研究[J]. 中华养生保健,2024,42(4):50-53.
[18] 王新颖,李家树,靳卫权,等.帕博利珠单抗联合诱导化疗、放疗对中晚期肺鳞癌患者有较好治疗效果[J]. 分子影像学杂志,2022,45(4):486-492.
[19] 郑大炜,郭娜,孙辉.调强放疗联合PD-1/PD-L1阻断疗法对中晚期非小细胞肺癌患者免疫状态及近期预后的影响[J]. 实用癌症杂志,2022,37(7):1165-1169.
[20] 李方,侯晓明,刘峥.同步推量调强放疗联合卡瑞利珠单抗治疗非小细胞肺癌的临床疗效及其机制研究[J]. 实用心脑肺血管病杂志,2021,29(11):96-101.
[21] 李聪,罗琼.帕博利珠单抗联合放化疗治疗晚期非小细胞肺癌患者的有效性研析[J]. 智慧健康,2023,9(17):187-190,194.
[22] 许德颖.帕博利珠单抗联合放化疗治疗晚期非小细胞肺癌患者的临床疗效与安全性[J]. 实用药物与临床,2022,25(3):232-235.
[23] ZHOU Q,CHEN M,JIANG O,et al.Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced,unresectable,stage Ⅲ non-small-cell lung cancer in China(GEMSTONE-301):interim results of a randomised,double-blind,multicentre,phase 3 trial[J]. Lancet Oncol,2022,23(2):209-219.
[24] PETERS S,PUJOL J L,DAFNI U,et al.Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy-results from the randomised phase Ⅱ ETOP/IFCT 4-12 STIMULI trial[J]. Ann Oncol,2022,33(1):67-79.
[25] PAKKALA S,HIGGINS K,CHEN Z,et al.Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer:a randomized phase Ⅱ study[J]. J Immunother Cancer,2020,8(2):e001302.
[26] SCHOENFELD J D,GIOBBIE-HURDER A,RANASINGHE S,et al.Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy:an open-label,multicentre,randomised,phase 2 trial[J]. Lancet Oncol,2022,23(2):279-291.
[27] THEELEN W S M E,PEULEN H M U,LALEZARI F,et al.Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer:results of the PEMBRO-RT phase 2 randomized clinical trial[J]. JAMA Oncol,2019,5(9):1276.
[28] ALTORKI N K,MCGRAW T E,BORCZUK A C,et al.Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer:a single-centre,randomised phase 2 trial[J]. Lancet Oncol,2021,22(6):824-835.
[29] CHANG J Y,LIN S H,DONG W,et al.Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer:an open-label,randomised,phase 2 trial[J]. Lancet,2023,402(10405):871-881.
[30] CHENG Y,SPIGEL D R,CHO B C,et al.Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer[J]. N Engl J Med,2024,391(14):1313-1327.
[31] SPIGEL D R,FAIVRE-FINN C,GRAY J E,et al.Five-year survival outcomes from the PACIFIC trial:durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer[J]. J Clin Oncol,2022,40(12):1301-1311.
[32] 王康馨,赵阳,闫婧.肿瘤放疗联合免疫检查点阻断治疗的应用进展[J]. 医学研究生学报,2019,32(6):637-641.
[33] CHEN X,LIU W,WANG Y,et al.Synergistic effects of radiotherapy and immunotherapy:improving oncological outcomes[J]. Front Immunol,2026,17:1771355.
[34] DAI J,MA L,HAN X,et al.Synergizing radiotherapy and immune checkpoint inhibitors in malignant solid tumours:mechanistic insights and translational frontiers[J]. Expert Rev Mol Med,2026,28:e17.
[35] WANG C,HAN L,ZHANG J,et al.Radiotherapy in combination with PD-1 and TIGIT blockade mediate antitumor abscopal effects and immune memory via CD8⁺ T cells[J]. Cancer Lett,2025,631:217935.
[36] MORIDIKIA A,MONTAZERSAHEB S,MOLAVI O.Manipulation of tumor microenvironment by induction of immunogeniccell death and immune check point inhibitors for enhancing the efficacy of cancer treatments[J]. Biomed Pharmacother,2026,196:119118.
[37] GENG Y,ZHANG Q,FENG S,et al.Safety and Efficacy of PD-1/PD-L1 inhibitors combined with radiotherapy in patients with non-small-cell lung cancer:a systematic review and meta-analysis[J]. Cancer Med,2021,10(4):1222-1239.
[38] ACKER F,RECK M,MARTIN D,et al.Efficacy and safety of immune checkpoint inhibition combined with concurrent chemoradiotherapy in patients with stage Ⅲ unresectable non-small cell lung cancer:a systematic review and meta-analysis[J]. Eur J Cancer,2025,218:115266.
[39] BRADLEY J D,SUGAWARA S,LEE K H,et al.Simultaneous durvalumab and platinum-based chemoradiotherapy in unresectable stage Ⅲ non-small cell lung cancer:the phase Ⅲ PACIFIC-2 study[J]. J Clin Oncol,2025,43:3610-3621.
[40] WEISMAN M,DURM G,SHIELDS M D,et al.Evaluation of radiation pneumonitis in a phase 2 study of consolidation immunotherapy with nivolumab and ipilimumab or nivolumab alone following concurrent chemoradiation therapy for unresectable stage ⅢA/ⅢB non-small cell lung cancer[J]. Int J Radiat Oncol,2025,121(3):720-727.
[41] 刘盼,孙志强,汪建林.立体定向放疗联合免疫治疗在实体肿瘤的研究进展[J]. 手术电子杂志,2024,11(4):36-43.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录