Antibiotic use alters commensal gut microbiota, which is a key regulator of immune homeostasis.
To investigate the impact of antibiotic use on clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with systemic agents.
We analyzed two cohorts: an institutional cohort (n=146) receiving programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) and a trial-database cohort (n=4144) receiving interferon-α (n=510), mammalian target of rapamycin (mTOR) inhibitors (n=660), and vascular endothelial growth factor targeted therapies (VEGF-TT; n=2974) on phase II/III clinical trials.
The association of antibiotic use (defined as use from 8 wk before to 4 wk after the initiation of anticancer therapy) with progression-free survival (PFS) and overall survival (OS) was evaluated using Cox regression, adjusted for known prognostic factors including International Metastatic RCC Database Consortium risk factors.
Most patients were male, had clear cell histology, and were at an intermediate risk. Overall, in the institutional cohort, objective response rate (ORR) was 30%, PFS was 7.2 mo, and 1-yr OS was 77%. Antibiotic users (n=31, 21%) had a lower ORR (12.9% vs 34.8%, p=0.026) and shorter PFS (adjusted hazard ratio [HR]=1.96, 95% confidence interval [CI] 1.20-3.20, p=0.007) than antibiotic nonusers. In the trial-database cohort, antibiotic use (n=709, 17%) adversely impacted OS in patients treated with interferon (HR=1.62, 95% CI 1.13-2.31, p=0.008) or with VEGF-TT and prior cytokines (HR=1.65, 95% CI 1.04-2.62, p=0.033), but not patients treated with mTOR inhibitors or VEGF-TT without prior cytokines. Limitations include retrospective design, and limited details regarding concomitant medications and antibiotic indication/duration.
Antibiotic use appears to reduce the efficacy of immunotherapy-based regimens in mRCC. The modulation of gut microbiota may play an important role in optimizing outcomes of patients treated with ICIs.
We evaluated metastatic renal cell carcinoma patients and found that those who were treated with immunotherapy had worse outcomes if they also received antibiotics at the start of treatment. This study highlights the importance of judicious antibiotic use.
European urology oncology. 2019 Sep 24 [Epub ahead of print]
Aly-Khan A Lalani, Wanling Xie, David A Braun, Marina Kaymakcalan, Dominick Bossé, John A Steinharter, Dylan J Martini, Ronit Simantov, Xun Lin, Xiao X Wei, Bradley A McGregor, Rana R McKay, Lauren C Harshman, Toni K Choueiri
Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Pharmacy and Clinical Support, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Medicine, Division of Medical Oncology, University of Ottawa, Ottawa, ON, Canada., Emory University School of Medicine, Atlanta, GA, USA., Pfizer Oncology, New York, NY, USA., Pfizer Oncology, San Diego, CA, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; University of California San Diego, Moores Cancer Center, San Diego, CA, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: .