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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (04) : 553 -557. doi: 10.3877/cma.j.issn.1674-6902.2024.04.009

论著

帕博利珠单抗治疗晚期非小细胞肺癌反应降低与抗生素预处理的关系
刘松1, 张进召1, 贾艳云1,†()   
  1. 1. 710077　西安，西安医学院第一附属医院呼吸与危重症医学科
  • 收稿日期:2024-02-22 出版日期:2024-08-25
  • 通信作者: 贾艳云
  • 基金资助:
    陕西省重点研发计划项目(2022SF-554)

Relationship between reduced response to pabolizumab in treatment of advanced non-small cell lung cancer and antibiotic preconditioning

Song Liu1, Jinzhao Zhang1, Yanyun Jia1,†()   

  1. 1. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi′an Medical University, Xi′an 710077, China
  • Received:2024-02-22 Published:2024-08-25
  • Corresponding author: Yanyun Jia
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引用本文：

刘松, 张进召, 贾艳云. 帕博利珠单抗治疗晚期非小细胞肺癌反应降低与抗生素预处理的关系[J]. 中华肺部疾病杂志(电子版), 2024, 17(04): 553-557.

Song Liu, Jinzhao Zhang, Yanyun Jia. Relationship between reduced response to pabolizumab in treatment of advanced non-small cell lung cancer and antibiotic preconditioning[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(04): 553-557.

目的

分析抗生素(antibiotic, ATB)预处理与晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者帕博利珠单抗治疗反应及预后的关系。

方法

选择2019年1月至2023年1月我院收治的接受帕博利珠单抗治疗92例晚期NSCLC患者，收集临床数据资料，根据治疗开始前30 d内是否接受ATB预处理，将接受ATB预处理17例为观察组，未接受75例为对照组。记录客观缓解率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、疾病进展、无进展生存期(progression-free survival, PFS)、总生存期(overall survival, OS)。

结果

对照组ORR 27例(36.00%)高于观察组2例(11.76%)(P>0.05)；对照组DCR 65例(84.00%)高于观察组8例(47.06%)(P<0.05)；对照组疾病进展26例(34.67%)低于观察组11例(64.71%)(P<0.05)；对照组预后不佳7例(9.33%)低于观察组11例(64.71%)(P<0.05)。经单因素分析，只有肿瘤最大直径≥2.40 cm(OR＝1.012，95%CI：1.004～1.951，P＝0.043)、ALB≥40.90 g/L(OR＝0.406，95%CI：0.172～0.955，P＝0.039)和ATB(＋)(OR＝2.614，95%CI：1.288～5.306，P＝0.008)是影响疾病进展的临床因素。多因素COX回归分析发现ATB预处理是病情进展及预后不佳相关的危险因素。Kaplan-Meier绘图分析ATB预处理与晚期NSCLC患者PFS的关系，观察组中位PFS 1.77(0.33～14.00)个月、中位OS 7.17(1.90～14.00)个月短于对照组5.43(0.70～14.03)个月，5.43(2.10～14.47)个月(P<0.05)。

结论

帕博利珠单抗治疗晚期NSCLC，治疗前30 d内ATB预处理与治疗后的反应降低具有意义。

关键词: 晚期非小细胞肺癌, 帕博利珠单抗, 抗生素, 治疗反应
Objective

To analyze the relationship between antibiotic (ATB) pretreatment and the therapeutic response and prognosis of pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC).

Methods

A total of 92 patients with advanced NSCLC treated with pembrolizumab in our hospital from January 2019 to January 2023 were retrospectively analyzed. The clinical data of the patients were collected, and the patients were divided into ATB (-) group and ATB (+ ) group according to whether they had received any ATB treatment within 30 days before pembrolizumab treatment. Objective response rate (ORR), disease control rate(DCR), disease progression, progression-free survival (PFS) and overall survival (OS) were recorded.

Results

There was no significant difference in ORR between the control group 27cases(36.00%) and the observation group 8 cases(11.76%)(P>0.05). The DCR in control group 65 cases(84.00%)was significantly higher than that in observation group 8 cases(47.06%)(P<0.05). Disease progression occurred in 26 patients(34.67%) in the control group and 11 patients(64.71%) in the observation group (P<0.05).Case fatality rate in control group 7 cases(9.33%) lower than observation group 11 cases(64.71%)(P<0.05). Multivariate COX regression analysis found that ATB(+ ) was the only independent risk factor associated with disease progression and death. Kaplan-Meier mapping analyzed the relationship between ATB preconditioning and PFS in patients with advanced NSCLC. The median PFS in the observation group [1.77(0.33~14.00)months vs. 5.43(0.70~14.03)months, P=0.006], the median OS [7.17(1.90~14.00)months vs. 5.43(2.10~14.47)months, P=0.016] was significantly shorter than that of the control group.

Conclusions

In advanced NSCLC patients treated with pembrolizumab, ATB pretreatment within 30 days before treatment is associated with reduced therapeutic response and shorter survival.

Key words: Advanced non-small cell lung cancer, Antibiotics, Pembrolizumab, Therapeutic response
表1 两组NSCLC患者的临床特征比较
临床资料 对照组(n＝75) 观察组(n＝17) Z/t/χ2 P值
临床分期[n(%)]     0.006 0.940
Ⅲ期 11(14.67) 2(11.76)    
Ⅳ期 64(85.33) 15(88.24)    
肿瘤最大直径[cm，M50(P25，P75)] 2.55(1.55，4.95) 3.55(2.45，8.40) －1.591 0.112
组织学类型[n(%)]     0.924 0.630
肺腺癌 38(50.67) 7(41.18)    
肺鳞癌 26(34.67) 6(35.29)    
其他 11(14.67) 4(23.53)    
治疗[n(%)]        
胸部放疗 20(26.67) 2(11.76) 1.691 0.193
根治性手术 15(20.00) 4(23.53) 0.105 0.746
实验室指标        
Hb[g/L，(±s)] 129.00±18.60 128.47±23.88 0.100 0.920
CRP[mg/dl，M50(P25，P75)] 0.28(0.10，0.40) 0.80(0.31，1.08) －3.095 0.002
ALP[U/L，(±s)] 91.17±22.03 101.12±30.62 1.557 0.123
PLR[M50(P25，P75)] 250.47(192.55，312.69) 182.16(147.93，318.02) －0.840 0.401
LDH[U/L，M50(P25，P75] 234.00(196.50，257.00) 265.50(208.50，321.50) －1.922 0.055
ALB[g/L，(±s)] 40.76±4.68 39.65±4.98 0.873 0.385
LMR[M50(P25，P75)] 1.32(0.99，1.54) 2.13(1.77，2.72) －1.212 0.225
PD-L1表达(免疫组化)     0.950 0.330
免疫组化评分≥1 30(40.0) 9(52.94)    
免疫组化评分<1 45(60.0) 8(47.06)    
图1 ATB预处理与晚期NSCLC患者PFS的关系
图2 ATB预处理与晚期NSCLC患者OS的关系
1
张雨峤，梅伟健. 免疫检查点抑制剂治疗实体瘤的标志性成果[J]. 实用医学杂志，2024, 40(2): 272-277.
2
Kok PS, Yoon WH, Lord S, et al. Tumor response end points as surrogates for overall survival in immune checkpoint inhibitor trials: a systematic review and meta-analysis[J]. JCO Precis Oncol, 2021, 5: 1151-1159.
3
Ma X, Zhang Y, Wang S, et al. Immune checkpoint inhibitor (ICI) combination therapy compared to monotherapy in advanced solid cancer: A systematic review[J]. J Cancer, 2021, 12(5): 1318-1333.
4
Li Y, Liang X, Li H, et al. Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: A systematic review and network meta-analysis[J]. Chin Med J (Engl), 2023, 136(18): 2156-2165.
5
Blanco R, Dómine M, González JL, et al. Pembrolizumab as first-line treatment for advanced NSCLC in older adults: A phase Ⅱ clinical trial evaluating geriatric and quality-of-life outcomes[J]. Lung Cancer, 2023, 183: 107318-107328.
6
Lurienne L, Cervesi J, Duhalde L, et al. NSCLC immunotherapy efficacy and antibiotic use: A systematic review and Meta-analysis[J]. J Thorac Oncol, 2020, 15(7): 1147-1159.
7
Simpson RC, Shanahan ER, Scolyer RA, et al. Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors[J]. Nat Rev Clin Oncol, 2023, 20(10): 697-715.
8
Yang L, Bajinka O, Jarju PO, et al. The varying effects of antibiotics on gut microbiota[J]. AMB Express, 2021, 11(1): 116-128.
9
Huang C, Feng S, Huo F, et al. Effects of four antibiotics on the diversity of the intestinal microbiota[J]. Microbiol Spectr, 2022, 10(2): e0190421-e0190431.
10
Preissner S, Heiland M, Preissner R, et al. Antibiotics significantly decrease the survival of head and neck carcinoma patients with immunotherapy: A real-world analysis of more than 3000 cases[J]. Cancers (Basel), 2023, 15(8): 2342-2351.
11
Nishino M, Wang X, Ricciuti B, et al. Advanced non-small-cell lung cancer treated with first-line pembrolizumab plus chemotherapy: tumor response dynamics as a marker for survival[J]. Eur Radiol, 2023, 33(10): 7284-7293.
12
Tsikala-Vafea M, Belani N, Vieira K, et al. Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis[J]. Int J Infect Dis, 2021, 106: 142-154.
13
Acharya M, Kim T, Li C. Broad-Spectrum antibiotic use and disease progression in early-stage melanoma patients: a retrospective cohort study[J]. Cancers (Basel), 2021, 13(17): 4367-4385.
14
Zhou J, Huang G, Wong W C, et al. The impact of antibiotic use on clinical features and survival outcomes of cancer patients treated with immune checkpoint inhibitors[J]. Front Immunol, 2022, 13: 968729.
15
Maesaka K, Sakamori R, Yamada R, et al. Pretreatment with antibiotics is associated with reduced therapeutic response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma[J]. PLoS One, 2023, 18(2): e0281459.
16
张静涛，刘子琛，纪凌云，等. 非小细胞肺癌免疫检查点抑制剂相关性肺炎研究进展及中西医结合治疗[J]. 中国免疫学杂志，2024, 40(1): 213-219.
17
Huang L, Guo Y, Liu S, et al. Targeting regulatory T cells for immunotherapy in melanoma[J]. Mol Biomed, 2021, 2(1): 11.
18
Dwivedi M, Tiwari S, Kemp EH, et al. Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics[J]. Heliyon, 2022, 8(8): e10450-e10461.
19
Churov A, Zhulai G. Targeting adenosine and regulatory T cells in cancer immunotherapy[J]. Hum Immunol, 2021, 82(4): 270-278.
20
Wang J, Yang HR, Wang DJ, et al. Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors[J]. Oncol Lett, 2020, 20(6): 342.
21
Lu Y, Yuan X, Wang M, et al. Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies[J]. J Hematol Oncol, 2022, 15(1): 47-66.
22
Varadé J, Magadán S, González-Fernández Á. Human immunology and immunotherapy: main achievements and challenges[J]. Cell Mol immuno1, 2021, 18(4): 805-828.
23
Hayase E, Jenq RR. Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer[J]. Genome Med, 2021, 13(1): 107.
24
Wu J, Wang S, Zheng B, et al. Modulation of gut microbiota to enhance effect of checkpoint inhibitor immunotherapy[J]. Front Immunol, 2021, 12: 669150-669160.
25
Patel P, Poudel A, Kafle S, et al. Influence of microbiome and antibiotics on the efficacy of immune checkpoint inhibitors[J]. Cureus, 2021, 13(8): e16829.
26
Zhang J, Dai Z, Yan C, et al. A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics[J]. Clin Transl Oncol, 2021, 23(12): 2415-2430.
27
Giordan Q, Salleron J, Vallance C, et al. Impact of antibiotics and proton pump inhibitors on efficacy and tolerance of anti-PD-1 immune checkpoint inhibitors[J]. Front Immunol, 2021, 12: 716317.
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