Antibiotics are associated with worse outcomes in lung cancer patients treated with chemotherapy and immunotherapy Journal Article
| Authors: | Elkrief, A.; Méndez-Salazar, E. O.; Maillou, J.; Vanderbilt, C. M.; Gogia, P.; Desilets, A.; Messaoudene, M.; Kelly, D.; Ladanyi, M.; Hellmann, M. D.; Zitvogel, L.; Rudin, C. M.; Routy, B.; Derosa, L.; Schoenfeld, A. J. |
| Article Title: | Antibiotics are associated with worse outcomes in lung cancer patients treated with chemotherapy and immunotherapy |
| Abstract: | Anti-PD(L)-1 inhibition combined with platinum doublet chemotherapy (Chemo-IO) has become the most frequently used standard of care regimen in patients with non-small cell lung cancer (NSCLC). The negative impact of antibiotics on clinical outcomes prior to anti-PD(L)-1 inhibition monotherapy (IO) has been demonstrated in multiple studies, but the impact of antibiotic exposure prior to initiation of Chemo-IO is controversial. We assessed antibiotic exposures at two time windows: within 60 days prior to therapy (-60 d window) and within 60 days prior to therapy and 42 days after therapy (-60 + 42d window) in 2028 patients with advanced NSCLC treated with Chemo-IO and IO monotherapy focusing on objective response rate (ORR: rate of partial response and complete response), progression-free survival (PFS), and overall survival (OS). We also assessed impact of antibiotic exposure in an independent cohort of 53 patients. Univariable and multivariable analyses were conducted along with a meta-analysis from similar studies. For the -60 d window, in the Chemo-IO group (N = 769), 183 (24%) patients received antibiotics. Antibiotic exposure was associated with worse ORR (27% vs 40%, p = 0.001), shorter PFS (3.9 months vs. 5.9 months, hazard ratio [HR] 1.35, 95%CI 1.1,1.6, p = 0.0012), as well as shorter OS (10 months vs. 15 months, HR 1.50, 95%CI 1.2,1.8, p = 0.00014). After adjusting for known prognostic factors in NSCLC, antibiotic exposure was independently associated with worse PFS (HR 1.39, 95%CI 1.35,1.7, p = 0.002) and OS (HR 1.61, 95%CI 1.28,2.03, p < 0.001). Similar results were obtained in the -60 + 42d window, and also in an independent cohort. In a meta-analysis of patients with NSCLC treated with Chemo-IO (N = 4) or IO monotherapy (N = 13 studies) antibiotic exposure before treatment was associated with worse OS among all patients (n = 11,351) (HR 1.93, 95% CI 1.52, 2.45) and Chemo-IO-treated patients (n = 1201) (HR 1.54, 95% CI 1.28, 1.84). Thus, antibiotics exposure prior to Chemo-IO is common and associated with worse outcomes, even after adjusting for other factors. These results highlight the need to implement antibiotic stewardship in routine oncology practice. © The Author(s) 2024. |
| Keywords: | cancer chemotherapy; controlled study; aged; antibiotic agent; major clinical study; overall survival; advanced cancer; monotherapy; outcome assessment; cancer immunotherapy; progression free survival; cohort analysis; lung cancer; practice guideline; oncology; sulfonamide; cephalosporin derivative; immune checkpoint inhibitor; antimicrobial stewardship; human; male; female; article; ecog performance status |
| Journal Title: | npj Precision Oncology |
| Volume: | 8 |
| ISSN: | 2397-768X |
| Publisher: | Springer Nature |
| Date Published: | 2024-07-16 |
| Start Page: | 143 |
| Language: | English |
| DOI: | 10.1038/s41698-024-00630-w |
| PROVIDER: | scopus |
| PMCID: | PMC11252311 |
| PUBMED: | 39014160 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Adam J. Schoenfeld -- Source: Scopus |
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1326Ladanyi -
411Hellmann -
488Rudin -
29Kelly -
135Vanderbilt -
131Schoenfeld -
41Elkrief -
3
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