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

Abstract

Background

The composition of gut microbiota affects anti-tumor 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-PD-(L)1 mAb monotherapy or combination at two academic institutions. Those receiving ATB within 30 days of beginning ICI were compared to 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 to no ATB was associated with increased risk of primary progressive disease (PD) (75% vs 22%, p < 0.01), shorter PFS (median 1.9 vs 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 vs 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% vs 43%, p = 0.26) but decreased PFS (median 1.9 vs 3.8 months, HR 1.5, 95% CI 1.0-2.2, p = 0.03) and OS (median 7.9 vs 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.