Meta-analysis of the efficacy of immune checkpoint inhibitors in the treatment of NSCLC with different <italic style="font-style: italic">KRAS</italic> genotypes

LIAO Wen; CHEN Wei; CHEN Jiayi; YU Junxian

doi:10.6039/j.issn.1001-0408.2023.24.18

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Meta-analysis of the efficacy of immune checkpoint inhibitors in the treatment of NSCLC with different KRAS genotypes

更新时间：2023-12-22

- Meta-analysis of the efficacy of immune checkpoint inhibitors in the treatment of NSCLC with different KRAS genotypes
- ZHONGGUO YAOFANG Vol. 34, Issue 24, Pages: 3055-3059(2023)
- 作者机构：
  
  1.首都医科大学附属北京友谊医院药学部，北京　100050
  2.应急总医院药学部，北京　100028
  3.首都医科大学护理学院，北京　100069
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.24.18
  CLC： R734.2;R979.1
- Published：30 December 2023，
  
  Received：08 May 2023，
  
  Revised：21 November 2023，
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廖雯,陈威,陈嘉怡等.免疫检查点抑制剂用于KRAS基因不同分型NSCLC疗效的Meta分析[J].中国药房,2023,34(24):3055-3059.

LIAO Wen,CHEN Wei,CHEN Jiayi,et al.Meta-analysis of the efficacy of immune checkpoint inhibitors in the treatment of NSCLC with different KRAS genotypes[J].ZHONGGUO YAOFANG,2023,34(24):3055-3059.
廖雯,陈威,陈嘉怡等.免疫检查点抑制剂用于KRAS基因不同分型NSCLC疗效的Meta分析[J].中国药房,2023,34(24):3055-3059. DOI： 10.6039/j.issn.1001-0408.2023.24.18.

LIAO Wen,CHEN Wei,CHEN Jiayi,et al.Meta-analysis of the efficacy of immune checkpoint inhibitors in the treatment of NSCLC with different KRAS genotypes[J].ZHONGGUO YAOFANG,2023,34(24):3055-3059. DOI： 10.6039/j.issn.1001-0408.2023.24.18.

摘要

目的

评价免疫检查点抑制剂（ICIs）用于鼠类肉瘤病毒癌基因（

KRAS

）基因不同分型非小细胞肺癌（NSCLC）的疗效。

方法

计算机检索PubMed、the Cochrane Library、Web of Science、Embase、中国知网、万方数据、维普网，收集ICIs单药或多种ICIs联用或ICIs联合传统化疗（试验组）对比传统化疗（对照组）用于NSCLC的随机对照试验（RCTs），检索时限为建库至2023年4月1日。筛选文献、提取数据和评价质量后，采用RevMan 5.4软件进行Meta分析、敏感性分析和发表偏倚分析。

结果

共纳入7项RCTs，合计5 980例患者。Meta分析结果显示，试验组患者的总生存期（OS）[HR＝0.79，95%CI（0.72，0.87），

＜0.000 01]、无进展生存期（PFS）[HR＝0.63，95%CI（0.50，0.80），

＝0.000 2]均显著长于对照组，且试验组

KRAS

突变型[HR＝0.63，95%CI（0.53，0.75），

＜0.000 01]、

KRAS

野生型[HR＝0.87，95%CI（0.78，0.98），

＝0.02]患者的OS，

KRAS

突变型[HR＝0.58，95%CI（0.43，0.78），

＝0.000 3]、

KRAS

野生型[HR＝0.68，95%CI（0.47，0.99），

＝0.04]患者的PFS均显著长于对照组；按不同治疗方案进行亚组分析的结果显示，试验组使用一、二线治疗方案，单用ICIs，使用ICIs联合传统化疗的

KRAS

突变型患者的OS，以及试验组使用一线治疗方案的

KRAS

突变型、

KRAS

野生型患者的PFS均显著长于对照组（

＜0.05）。敏感性分析结果显示，本研究所得结果较稳健。发表偏倚结果显示，本研究存在发表偏倚的可能性较小。

结论

ICIs用于NSCLC患者的疗效显著，且无论是否发生

KRAS

突变，NSCLC患者都同样受益。

Abstract

OBJECTIVE

To evaluate the efficacy of immune checkpoint inhibitors （ICIs） in the treatment of non-small cell lung cancer （NSCLC） with different

KRAS

genotypes.

METHODS

Retrieved from PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） about ICIs alone， combined use of various ICIs or ICIs combined with traditional chemotherapy （trial group） versus traditional chemotherapy （control group） for NSCLC were collected from the inception of the databases to April 1， 2023. After screening literature， extracting data and evaluating quality， meta-analysis， sensitivity analysis and publication bias analysis were conducted by using RevMan 5.4 software.

RESULTS

A total of 7 RCTs involving 5 980 patients were included. The results of the meta-analysis showed that overall survival （OS） [HR＝0.79， 95%CI （0.72， 0.87），

＜0.000 01] and progression-free survival （PFS） [HR＝0.63， 95%CI （0.50， 0.80），

＝0.000 2] of trial group were significantly longer than those of control group； furthermore， the OS of

KRAS

mutant type [HR＝0.63， 95%CI （0.53， 0.75），

＜0.000 01] and

KRAS

wild type [HR＝0.87， 95%CI （0.78， 0.98），

＝0.02]， PFS of

KRAS

mutant type [HR＝0.58， 95%CI （0.43， 0.78），

＝0.000 3] and

KRAS

wild type [HR＝0.68， 95%CI （0.47， 0.99），

＝0.04] in the trial group were all significantly longer than in the control group. Subgroup analysis by different treatment regimens showed that the OS of

KRAS

mutant type patients receiving first- and second-line treatment regimens， using ICIs alone and those receiving ICIs combined with traditional chemotherapy as well as PFS of

KRAS

mutant type and wild type patients receiving first-line treatment regimens in the trial group were all significantly longer than in the control group （

＜0.05）. Sensitivity analysis results indicated that the findings of this study were robust. Publication bias results showed that the possibility of publication bias in this study was small.

CONCLUSIONS

ICIs show significant efficacy in NSCLC patients， and NSCLC patients benefit equally regardless of whether

KRAS

mutations occur.

关键词

免疫检查点抑制剂非小细胞肺癌鼠类肉瘤病毒癌基因疗效

Keywords

non-small cell lung cancerKRASefficacy

references

SUNG H，FERLAY J，SIEGEL R L，et al. Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin，2021，71（3）：209-249.

SIEGEL R L，MILLER K D，FUCHS H E，et al. Cancer statistics，2021[J]. CA Cancer J Clin，2021，71（1）：7-33.

GOLDSTRAW P，CHANSKY K，CROWLEY J，et al. The IASLC lung cancer staging project：proposals for revision of the TNM stage groupings in the forthcoming（eighth）edition of the TNM classification for lung cancer[J]. J Thorac Oncol，2016，11（1）：39-51.

HUDSON K，CROSS N，JORDAN-MAHY N，et al. The extrinsic and intrinsic roles of PD-L1 and its receptor PD-1：implications for immunotherapy treatment[J]. Front Immunol，2020，11：568931.

TOPALIAN S L，DRAKE C G，PARDOLL D M. Targeting the PD-1/B7-H1（PD-L1）pathway to activate anti-tumor immunity[J]. Curr Opin Immunol，2012，24（2）：207-212.

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.

JOTTE R，CAPPUZZO F，VYNNYCHENKO I，et al. Atezolizumab in combination with carboplatin and nab-paclitaxel in advanced squamous NSCLC（IMpower131）：results from a randomized phase Ⅲ trial[J]. J Thorac Oncol，2020，15（8）：1351-1360.

BUDAY L，DOWNWARD J. Many faces of ras activation[J]. Biochim Biophys Acta，2008，1786（2）：178-187.

BOS J L. Ras oncogenes in human cancer：a review[J]. Cancer Res，1989，49（17）：4682-4689.

ADDERLEY H，BLACKHALL F H，LINDSAY C R. KRAS-mutant non-small cell lung cancer：converging small molecules and immune checkpoint inhibition[J]. EBioMedicine，2019，41：711-716.

GREEN S，HIGGINS J P. Preparing a cochrane review[M]//Cochrane Handbook for Systematic Reviews of Inter‐ventions. Chichester，UK：John Wiley & Sons，Ltd.，2008：11-30.

BORGHAEI H，PAZ-ARES L，HORN L，et al. Nivo-lumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer[J]. N Engl J Med，2015，373（17）：1627-1639.

HELLMANN M D，PAZ-ARES L，BERNABE CARO R，et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer[J]. N Engl J Med，2019，381（21）：2020-2031.

SOCINSKI M A，JOTTE R M，CAPPUZZO F，et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC[J]. N Engl J Med，2018，378（24）：2288-2301.

HERBST R S，LOPES G，KOWALSKI D M，et al. LBA4 association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in keynote-042[J]. Ann Oncol，2019，30：Ⅺ63-Ⅺ64.

GADGEEL S，RODRIGUEZ-ABREU D，FELIP E，et al. KRAS mutational status and efficacy in keynote-189：pembrolizumab（pembro）plus chemotherapy（chemo）vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC[J]. Ann Oncol，2019，30：Ⅺ64-Ⅺ65.

RITTMEYER A，BARLESI F，WATERKAMP D，et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer（OAK）：a phase 3，open-label，multicentre randomised controlled trial[J]. Lancet，2017，389（10066）：255-265.

FEHRENBACHER L，SPIRA A，BALLINGER M，et al. Atezolizumab versus docetaxel for patients with pre-viously treated non-small-cell lung cancer（POPLAR）：a multicentre，open-label，phase 2 randomised controlled trial[J]. Lancet，2016，387（10030）：1837-1846.

IPPOLITO M R，MARTIS V，MARTIN S，et al. Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy[J]. Dev Cell，2021，56（17）：2440-2454.e6.

HARGADON K M，JOHNSON C E，WILLIAMS C J. Immune checkpoint blockade therapy for cancer：an overview of FDA-approved immune checkpoint inhibitors[J]. Int Immunopharmacol，2018，62：29-39.

RECK M，CARBONE D P，GARASSINO M，et al. Targeting KRAS in non-small-cell lung cancer：recent progress and new approaches[J]. Ann Oncol，2021，32（9）：1101-1110.

MASCAUX C，IANNINO N，MARTIN B，et al. The role of RAS oncogene in survival of patients with lung cancer：a systematic review of the literature with meta-analysis[J]. Br J Cancer，2005，92（1）：131-139.

OSTA B E，BEHERA M，KIM S，et al. Characteristics and outcomes of patients with metastatic KRAS-mutant lung adenocarcinomas：the lung cancer mutation consortium experience[J]. J Thorac Oncol，2019，14（5）：876-889.

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⁰

Meta-analysis of the efficacy of immune checkpoint inhibitors in the treatment of NSCLC with different KRAS genotypes

DOI：10.6039/j.issn.1001-0408.2023.24.18

摘要

Abstract

关键词

Keywords

references