Antibiotics Could Reduce Diarrhea, Improve Outcomes in Metastatic RCC

The incidental use of antibiotics among patients with metastatic renal cell carcinoma (RCC) taking vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKIs) was associated with improved progression-free survival, according to the results of a study presented at the 2018 Genitourinary Cancers Symposium.

Prior research had shown that higher levels of stool Bacteroides were found in patients with metastatic RCC experiencing diarrhea on VEGF TKI therapy. Diarrhea while on VEGF receptor TKIs can result in dose reductions and reduced drug efficacy. For this study, Camryn Froerer, a fourth-year PharmD student at the University of Utah, Salt Lake City, and colleagues hypothesized that use and duration of antibiotics targeting Bacteroides may decrease diarrhea and as a result increase VEGF TKI dose intensity, improving survival outcomes.

“In these hypotheses-generating data, use of Bacteroides-targeting antibiotics resulted in a progression-free survival hazard ratio of 0.92, which translates to an 8% decrease in risk for progression for each additional day of Bacteroides-targeting antibodies prescribed compared to those with no antibiotics,” Froerer said during his presentation. “Thus the duration of antibiotics appeared to be a key factor in improving progression-free survival in patients with metastatic RCC.”

In this retrospective analysis, the researchers studied 145 patients diagnosed with intermediate-risk or poor-risk metastatic RCC who were taking first-line VEGF receptor TKIs between 2005 and 2017. They compared outcomes among patients who had no antibiotics prescribed (n = 96), those who received Bacteroides-targeting antibiotics (n = 17), and those who had received non–Bacteroides-targeting antibiotics within 30 days prior to or during VEGF TKI therapy (n = 32).

The 17 patients who received Bacteroides-targeting antibiotics had a median progression-free survival of 18 months compared with 8 months in patients with no antibiotic use. Results trended toward, but did not reach, statistical significance (P = .059), Froerer noted. Median progression-free survival among patients who received non–Bacteroides-targeting antibiotics was 9 months.

Froerer noted several study limitations, including its small sample size and a lack of data on the accurate grading and severity of diarrhea.

Future directions of research could focus on the development of clinical trials with antibiotics targeting stool Bacteroides, to manipulate the stool microbiome to improve outcomes in patients with metastatic RCC receiving VEGF TKIs.