Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade
Copyright © 2022 Elsevier Ltd. All rights reserved..
BACKGROUND: We previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications.
MATERIALS AND METHODS: We evaluated the prognostic ability of a "drug score" computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival.
RESULTS: Among the 293 eligible patients, good (19.5 months), intermediate (13.4 months), and poor (3.7 months) risk groups displayed a significantly different overall survival (OS) (log-rank test for trend: p = 0.016), but with a limited diagnostic ability (C-index: 0.57, 95%CI: 0.53-0.61), while no significant impact on progression-free survival (PFS) was reported (log-rank test for trend: p = 0.080; C-index: 0.55, 95%CI: 0.52-0.58). Considering the impact of the probiotics∗antibiotics interaction (p-value 0.0510) on OS, we implemented the drug score by assigning 0 points to concomitant antibiotics and probiotics. With the adapted drug score good, intermediate, and poor risk patients achieved a median OS of 19.6 months, 13.1 months, and 3.7 months, respectively, with a similar diagnostic ability (log-rank test for trend: p = 0.006; C-index: 0.58, 95%CI: 0.54-0.61). However, the diagnostic ability for PFS of the adapted score was improved (log-rank test for trend: p = 0.034; C-index: 0.62, 95%CI: 0.54-0.69).
CONCLUSIONS: Although we failed to validate the drug score in this independent Japanese cohort, we showed that probiotics may have an antibiotic-dependent impact on its prognostic value. Further investigation looking at the effect of concomitant medications and probiotics across cohorts of different ethnicities is warranted.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:172 |
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| Enthalten in: |
European journal of cancer (Oxford, England : 1990) - 172(2022) vom: 03. Sept., Seite 199-208 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Takada, Kazuki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.08.2022 Date Revised 08.11.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejca.2022.06.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Takada, Kazuki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 16.08.2022 | ||
| 500 | |a Date Revised 08.11.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: We previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications | ||
| 520 | |a MATERIALS AND METHODS: We evaluated the prognostic ability of a "drug score" computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival | ||
| 520 | |a RESULTS: Among the 293 eligible patients, good (19.5 months), intermediate (13.4 months), and poor (3.7 months) risk groups displayed a significantly different overall survival (OS) (log-rank test for trend: p = 0.016), but with a limited diagnostic ability (C-index: 0.57, 95%CI: 0.53-0.61), while no significant impact on progression-free survival (PFS) was reported (log-rank test for trend: p = 0.080; C-index: 0.55, 95%CI: 0.52-0.58). Considering the impact of the probiotics∗antibiotics interaction (p-value 0.0510) on OS, we implemented the drug score by assigning 0 points to concomitant antibiotics and probiotics. With the adapted drug score good, intermediate, and poor risk patients achieved a median OS of 19.6 months, 13.1 months, and 3.7 months, respectively, with a similar diagnostic ability (log-rank test for trend: p = 0.006; C-index: 0.58, 95%CI: 0.54-0.61). However, the diagnostic ability for PFS of the adapted score was improved (log-rank test for trend: p = 0.034; C-index: 0.62, 95%CI: 0.54-0.69) | ||
| 520 | |a CONCLUSIONS: Although we failed to validate the drug score in this independent Japanese cohort, we showed that probiotics may have an antibiotic-dependent impact on its prognostic value. Further investigation looking at the effect of concomitant medications and probiotics across cohorts of different ethnicities is warranted | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Concomitant medications | |
| 650 | 4 | |a Ethnicity | |
| 650 | 4 | |a Immune checkpoint inhibitors | |
| 650 | 4 | |a Microbiota | |
| 650 | 4 | |a Non-small cell lung cancer | |
| 650 | 4 | |a Probiotics | |
| 650 | 4 | |a Racial | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 700 | 1 | |a Buti, Sebastiano |e verfasserin |4 aut | |
| 700 | 1 | |a Bersanelli, Melissa |e verfasserin |4 aut | |
| 700 | 1 | |a Shimokawa, Mototsugu |e verfasserin |4 aut | |
| 700 | 1 | |a Takamori, Shinkichi |e verfasserin |4 aut | |
| 700 | 1 | |a Matsubara, Taichi |e verfasserin |4 aut | |
| 700 | 1 | |a Takenaka, Tomoyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Okamoto, Tatsuro |e verfasserin |4 aut | |
| 700 | 1 | |a Hamatake, Motoharu |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuchiya-Kawano, Yuko |e verfasserin |4 aut | |
| 700 | 1 | |a Otsubo, Kohei |e verfasserin |4 aut | |
| 700 | 1 | |a Nakanishi, Yoichi |e verfasserin |4 aut | |
| 700 | 1 | |a Okamoto, Isamu |e verfasserin |4 aut | |
| 700 | 1 | |a Pinato, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Cortellini, Alessio |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshizumi, Tomoharu |e verfasserin |4 aut | |
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