Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer - PubMed (original) (raw)

. 2018 Jun 1;29(6):1437-1444.

doi: 10.1093/annonc/mdy103.

M D Hellmann 2, M Spaziano 3, D Halpenny 4, M Fidelle 1, H Rizvi 5, N Long 4, A J Plodkowski 4, K C Arbour 6, J E Chaft 7, J A Rouche 8, L Zitvogel 9, G Zalcman 10, L Albiges 11, B Escudier 12, B Routy 13

Affiliations

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

L Derosa et al. Ann Oncol. 2018.

Abstract

Background: The composition of gut microbiota affects antitumor immune responses, preclinical and clinical outcome following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may affect effectiveness of ICI.

Patients and methods: We examined patients with advanced renal cell carcinoma (RCC) and non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy or combination at two academic institutions. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression-free survival (PFS) determined by RECIST1.1 and overall survival (OS) were assessed.

Results: Sixteen of 121 (13%) RCC patients and 48 of 239 (20%) NSCLC patients received ATB. The most common ATB were β-lactam or quinolones for pneumonia or urinary tract infections. In RCC patients, ATB compared with no ATB was associated with increased risk of primary progressive disease (PD) (75% versus 22%, P < 0.01), shorter PFS [median 1.9 versus 7.4 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.4-6.9, P < 0.01], and shorter OS (median 17.3 versus 30.6 months, HR 3.5, 95% CI 1.1-10.8, P = 0.03). In NSCLC patients, ATB was associated with similar rates of primary PD (52% versus 43%, P = 0.26) but decreased PFS (median 1.9 versus 3.8 months, HR 1.5, 95% CI 1.0-2.2, P = 0.03) and OS (median 7.9 versus 24.6 months, HR 4.4, 95% CI 2.6-7.7, P < 0.01). In multivariate analyses, the impact of ATB remained significant for PFS in RCC and for OS in NSCLC.

Conclusion: ATB were associated with reduced clinical benefit from ICI in RCC and NSCLC. Modulatation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.

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Figures

Figure 1.

Figure 1.

Best overall response (A), progression-free survival (PFS) (B), and overall survival (OS) (C) in patients with RCC treated with ICI, stratified by use of ATB within 30 days of initiating ICI. Best overall response (D), PFS (E), and OS (F) in patients with NSCLC treated with ICI, stratified by use of ATB within 30 days of initiating ICI._P_-values calculated with chi-squared and log-rank tests.

Figure 2.

Figure 2.

Subgroup analyses of independent prognostic factors for PFS (A and B) and OS (C and D) stratification in RCC and NSCLC, respectively. _P_-value for interaction calculated with Cox proportional hazards model.

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