Effect of antibiotic treatment on immune checkpoint inhibitors efficacy in patients with advanced non-small cell lung cancer

被引：6

作者：

Sen, Guelin Alkan ^{[1
]}

Oztas, Nihan Senturk ^{[1
]}

Degerli, Ezgi ^{[1
]}

Can, Gunay ^{[2
]}

Turna, Hande ^{[1
]}

Ozguroglu, Mustafa ^{[1
]}

机构：

[1] Istanbul Univ Cerrahpasa, Cerrahpasa Med Fac, Dept Internal Med, Div Med Oncol, Istanbul, Turkiye

[2] Istanbul Univ Cerrahpasa, Cerrahpasa Fac Med, Dept Publ Hlth, Istanbul, Turkiye

来源：

LUNG CANCER | 2023年 / 184卷

关键词：

Non small cell lung cancer; Antibiotics; Immune check point inhibitors; ATEZOLIZUMAB; CHEMOTHERAPY; MICROBIOME; NIVOLUMAB; DOCETAXEL; OAK;

D O I：

10.1016/j.lungcan.2023.107347

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Gut microbiota plays a crucial role in immune response. Recent data have shown that antibiotic (ATB) usage influences efficacy of immune check point inhibitors (ICIs) via altering microbiota of the gut.Methods: We retrospectively analyzed patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs as monotherapy or combination with chemotherapy (ChT) at the one academic center. Those receiving ATB for the first 12 weeks of the initiation of ICIs were compared with those who did not. The primary objective of this study was to assess the impact of ATB use on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) during ICIs therapy.Results: 90 patients were included in our analysis. Of these 90 patients, 27 (30%) received ATB in the first 12 weeks of the treatment. In patients who received ATB in the first 12 weeks of ICIs administration, PFS was significantly shorter (4.9 vs. 24.8 months, HR 2.52, 95% CI (1.52-4.18), p < 0.001). OS was also significantly shorter (5.4 vs. 37.8 months, HR 2.55, 95% CI (1.48-4.40), p = 0.001). We also examined the impact of ATB on ORR. Exposure to ATB for the first weeks consistently worsened the response rate; the ORR was 25.9% in the ATB group and 55.6% in the no ATB group (p = 0.01).Conclusion: Our findings demonstrated that the use of antibiotics around ICIs initiation was associated with decreased OS, PFS, and ORR in patients with NSCLC. This suggests that microbiota diversity may be one of the factors predicting the efficacy of ICIs.

引用

页数：7

共 27 条

[1] Use of broad-spectrum antibiotics impacts outcome in patients treated with immune checkpoint inhibitors [J].

Ahmed, Jibran ;

Kumar, Arun ;

Parikh, Kaushal ;

Anwar, Asad ;

Knoll, Bettina M. ;

Puccio, Carmelo ;

Chun, Hoo ;

Fanucchi, Michael ;

Lim, Seah H. .

ONCOIMMUNOLOGY, 2018, 7 (11)

[2] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[3] Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) [J].

Brueckl, Wolfgang M. ;

Ficker, Joachim H. ;

Zeitler, Gloria .

BMC CANCER, 2020, 20 (01)

[4] First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer [J].

Carbone, D. P. ;

Reck, M. ;

Paz-Ares, L. ;

Creelan, B. ;

Horn, L. ;

Steins, M. ;

Felip, E. ;

van den Heuvel, M. M. ;

Ciuleanu, T. -E. ;

Badin, F. ;

Ready, N. ;

Hiltermann, T. J. N. ;

Nair, S. ;

Juergens, R. ;

Peters, S. ;

Minenza, E. ;

Wrangle, J. M. ;

Rodriguez-Abreu, D. ;

Borghaei, H. ;

Blumenschein, G. R. ;

Villaruz, L. C. ;

Havel, L. ;

Krejci, J. ;

Corral Jaime, J. ;

Chang, H. ;

Geese, W. J. ;

Bhagavatheeswaran, P. ;

Chen, A. C. ;

Socinski, M. A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (25) :2415-2426

[5]

Chalabi M, 2020, ANN ONCOL, V31, P525, DOI [10.1016/j.annonc.2020.01.006, 10.1016/j.annoc.2020.01.006]

[6] Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer [J].

Derosa, L. ;

Hellmann, M. D. ;

Spaziano, M. ;

Halpenny, D. ;

Fidelle, M. ;

Rizvi, H. ;

Long, N. ;

Plodkowski, A. J. ;

Arbour, K. C. ;

Chaft, J. E. ;

Rouche, J. A. ;

Zitvogel, L. ;

Zalcman, G. ;

Albiges, L. ;

Escudier, B. ;

Routy, B. .

ANNALS OF ONCOLOGY, 2018, 29 (06) :1437-1444

[7] Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation [J].

Dethlefsen, Les ;

Relman, David A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 :4554-4561

[8] Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors [J].

Elkrief, Arielle ;

El Raichani, Layal ;

Richard, Corentin ;

Messaoudene, Meriem ;

Belkaid, Wiam ;

Malo, Julie ;

Belanger, Karl ;

Miller, Wilson ;

Jamal, Rahima ;

Letarte, Nathalie ;

Wong, Philip ;

Routy, Bertrand .

ONCOIMMUNOLOGY, 2019, 8 (04)

[9]

Fares Charlene M, 2019, Am Soc Clin Oncol Educ Book, V39, P147, DOI 10.1200/EDBK_240837

[10] Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients [J].

Gopalakrishnan, V. ;

Spencer, C. N. ;

Nezi, L. ;

Reuben, A. ;

Andrews, M. C. ;

Karpinets, T. V. ;

Prieto, P. A. ;

Vicente, D. ;

Hoffman, K. ;

Wei, S. C. ;

Cogdill, A. P. ;

Zhao, L. ;

Hudgens, C. W. ;

Hutchinson, D. S. ;

Manzo, T. ;

de Macedo, M. Petaccia ;

Cotechini, T. ;

Kumar, T. ;

Chen, W. S. ;

Reddy, S. M. ;

Sloane, R. Szczepaniak ;

Galloway-Pena, J. ;

Jiang, H. ;

Chen, P. L. ;

Shpall, E. J. ;

Rezvani, K. ;

Alousi, A. M. ;

Chemaly, R. F. ;

Shelburne, S. ;

Vence, L. M. ;

Okhuysen, P. C. ;

Jensen, V. B. ;

Swennes, A. G. ;

McAllister, F. ;

Sanchez, E. Marcelo Riquelme ;

Zhang, Y. ;

Le Chatelier, E. ;

Zitvogel, L. ;

Pons, N. ;

Austin-Breneman, J. L. ;

Haydu, L. E. ;

Burton, E. M. ;

Gardner, J. M. ;

Sirmans, E. ;

Hu, J. ;

Lazar, A. J. ;

Tsujikawa, T. ;

Diab, A. ;

Tawbi, H. ;

Glitza, I. C. .

SCIENCE, 2018, 359 (6371) :97-103

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