Associations between dysbiosis-inducing drugs, overall survival and tumor response in patients treated with immune checkpoint inhibitors.
antibiotic
drug-induced dysbiosis
dysbiosis
immune checkpoint inhibitor
melanoma
Journal
Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808
Informations de publication
Date de publication:
2021
2021
Historique:
received:
02
01
2021
accepted:
10
02
2021
entrez:
2
4
2021
pubmed:
3
4
2021
medline:
3
4
2021
Statut:
epublish
Résumé
There are conflicting data on the effects of dysbiosis-inducing drugs, and especially antibiotics (ATBs), on clinical outcomes in patients treated with immune checkpoint inhibitors (ICIs). There is a particular lack of data for patients with melanoma. We performed a single-center retrospective study of the associations between ATBs and other drugs known to modify the gut microbiota (proton pump inhibitors, nonsteroidal anti-inflammatory drugs, statins, opioids, anti-vitamin K, levothyroxine, vitamin D3, antiarrhythmics, metformin and phloroglucinol), overall survival (OS) and tumor response in consecutive cancer patients (particularly those with melanoma) treated with an ICI (ipilimumab, nivolumab or pembrolizumab) over a 9-year period. A total of 372 patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Overall, 112 patients (30.1%) had received ATBs. ATB use was associated with (1) shorter OS in the study population as a whole [adjusted hazard ratio [95% confidence interval (CI)]: 1.38 (1.00-1.90), Unlike other dysbiosis-inducing drugs, ATBs were associated with poorer clinical outcomes in ICI-treated patients overall and in the subset of patients with melanoma.
Sections du résumé
BACKGROUND
BACKGROUND
There are conflicting data on the effects of dysbiosis-inducing drugs, and especially antibiotics (ATBs), on clinical outcomes in patients treated with immune checkpoint inhibitors (ICIs). There is a particular lack of data for patients with melanoma.
METHODS
METHODS
We performed a single-center retrospective study of the associations between ATBs and other drugs known to modify the gut microbiota (proton pump inhibitors, nonsteroidal anti-inflammatory drugs, statins, opioids, anti-vitamin K, levothyroxine, vitamin D3, antiarrhythmics, metformin and phloroglucinol), overall survival (OS) and tumor response in consecutive cancer patients (particularly those with melanoma) treated with an ICI (ipilimumab, nivolumab or pembrolizumab) over a 9-year period.
RESULTS
RESULTS
A total of 372 patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Overall, 112 patients (30.1%) had received ATBs. ATB use was associated with (1) shorter OS in the study population as a whole [adjusted hazard ratio [95% confidence interval (CI)]: 1.38 (1.00-1.90),
CONCLUSION
CONCLUSIONS
Unlike other dysbiosis-inducing drugs, ATBs were associated with poorer clinical outcomes in ICI-treated patients overall and in the subset of patients with melanoma.
Identifiants
pubmed: 33796151
doi: 10.1177/17588359211000591
pii: 10.1177_17588359211000591
pmc: PMC7968039
doi:
Types de publication
Journal Article
Langues
eng
Pagination
17588359211000591Informations de copyright
© The Author(s), 2021.
Déclaration de conflit d'intérêts
Conflict of interest statement: The authors declare that there is no conflict of interest.
Références
Oncotarget. 2018 Mar 27;9(23):16512-16520
pubmed: 29662663
Aliment Pharmacol Ther. 2018 Feb;47(3):332-345
pubmed: 29205415
J Clin Oncol. 2015 Oct 1;33(28):3193-8
pubmed: 26282644
Crit Care Med. 2003 Apr;31(4):1250-6
pubmed: 12682500
Ann Oncol. 2020 Apr;31(4):525-531
pubmed: 32115349
Science. 2015 Nov 27;350(6264):1084-9
pubmed: 26541606
J Steroid Biochem Mol Biol. 2020 Jun;200:105663
pubmed: 32194242
Oncologist. 2020 Jan;25(1):55-63
pubmed: 31292268
Oncol Lett. 2019 Mar;17(3):2946-2952
pubmed: 30854072
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Nature. 2018 Mar 29;555(7698):623-628
pubmed: 29555994
Psychopharmacology (Berl). 2019 May;236(5):1411-1432
pubmed: 30806744
Oncologist. 2008;13 Suppl 4:2-9
pubmed: 19001145
Clin Transl Oncol. 2020 Sep;22(9):1481-1490
pubmed: 31919759
Ann Oncol. 2018 Jun 1;29(6):1437-1444
pubmed: 29617710
Eur Urol. 2020 Oct;78(4):540-543
pubmed: 32660748
Cancers (Basel). 2019 Jan 03;11(1):
pubmed: 30609850
J Clin Oncol. 2019 Aug 1;37(22):1927-1934
pubmed: 31206316
Thorac Cancer. 2020 Feb;11(2):353-361
pubmed: 31828967
Gut. 2016 May;65(5):749-56
pubmed: 26719299
Surg Oncol Clin N Am. 2015 Apr;24(2):215-27
pubmed: 25769707
J Immunother Cancer. 2019 Nov 6;7(1):287
pubmed: 31694714
Microbiome. 2017 Aug 9;5(1):95
pubmed: 28793934
J Infect. 2019 Dec;79(6):471-489
pubmed: 31629863
J Clin Oncol. 2018 Oct 1;36(28):2872-2878
pubmed: 30125216
Pharmacol Res Perspect. 2020 Jun;8(3):e00601
pubmed: 32476298
Clin Microbiol Infect. 2016 Feb;22(2):178.e1-178.e9
pubmed: 26482265
J Chronic Dis. 1987;40(5):373-83
pubmed: 3558716
Gut. 2016 May;65(5):740-8
pubmed: 26657899
Front Pharmacol. 2017 Aug 23;8:561
pubmed: 28878676
Melanoma Res. 2016 Dec;26(6):609-615
pubmed: 27603551
JAMA Netw Open. 2019 May 3;2(5):e192535
pubmed: 31050774
Cancer Treat Rev. 2014 Oct;40(9):1056-64
pubmed: 25060490
Anticancer Res. 2019 Nov;39(11):6265-6271
pubmed: 31704856
Clin Cancer Res. 2020 Oct 15;26(20):5487-5493
pubmed: 32933995
Hum Vaccin Immunother. 2018;14(9):2178-2182
pubmed: 29494275
Semin Cancer Biol. 2020 Oct;65:164-175
pubmed: 31911189
Aliment Pharmacol Ther. 2017 Jan;45(2):319-331
pubmed: 27868217
Clin Cancer Res. 2016 Feb 15;22(4):886-94
pubmed: 26446948
Mediators Inflamm. 2017;2017:3264217
pubmed: 28848246
Diabetologia. 2017 Sep;60(9):1662-1667
pubmed: 28770326
World J Gastroenterol. 2019 Jun 14;25(22):2706-2719
pubmed: 31235994
J Thorac Oncol. 2018 Nov;13(11):1771-1775
pubmed: 29935305
Anticancer Res. 2020 Jan;40(1):551-556
pubmed: 31892611
J Clin Oncol. 2015 Mar 1;33(7):773-81
pubmed: 25605840
Nat Med. 2017 Jul;23(7):850-858
pubmed: 28530702
Clin Ther. 2019 Jan;41(1):59-67
pubmed: 30528047
Science. 2015 Nov 27;350(6264):1079-84
pubmed: 26541610
Science. 2018 Jan 5;359(6371):91-97
pubmed: 29097494
Med Sci (Paris). 2016 Nov;32(11):961-967
pubmed: 28008836
Anesth Analg. 2007 Aug;105(2):524-7
pubmed: 17646517
Nature. 2017 Jan 18;541(7637):321-330
pubmed: 28102259
J Cell Physiol. 2019 Feb 20;:
pubmed: 30786013
Eur J Dermatol. 2015 Jan-Feb;25(1):36-44
pubmed: 25500362
Anticancer Res. 2017 Jun;37(6):3195-3200
pubmed: 28551664