Antibiotics Reduced Efficacy of Checkpoint Inhibitors in RCC, NSCLC

April 16, 2018

Antibiotics administered within 30 days of starting immunotherapy reduced both PFS and OS for patients with advanced RCC and NSCLC.

Use of antibiotics may be associated with reduced effectiveness of immune checkpoint inhibitors (ICIs) for patients with advanced renal cell carcinoma (RCC) and non–small-cell lung cancer (NSCLC), according to the results of a study published in Annals of Oncology.

In the study, patients who had received antibiotics within 30 days of beginning immunotherapy had worse progression-free survival (PFS) and overall survival (OS) compared with patients who were not being treated with antibiotics.

“These results confirm that antibiotics-associated dysbiosis might be deleterious in patients treated with immune checkpoint inhibitors, suggesting that an intact gut microbiota is needed to mobilize the immune system regardless of the tumor site,” wrote Lisa Derosa, MD, of Gustave Roussy Cancer Campus, Villejuif, France, and colleagues. “Efforts to improve antibiotic stewardship are already ongoing to prevent the emergence of multidrug-resistant organisms, which can be particularly dangerous for cancer patients. The data in this report may add additional incentive to avoid unnecessary antibiotics.”

Using data from two academic institutions, Derosa and colleagues compared outcomes in patients with advanced RCC or NSCLC who had received antibiotics within 30 days of beginning immunotherapy against outcomes in those who did not. Of 121 patients with RCC, 13% had received antibiotics, while 20% of the 239 patients with NSCLC had received antibiotics.

Among patients with RCC, having taken antibiotics was associated with a significantly increased risk for progressive disease (75% vs 22%; P < .01) compared with not taking them. In addition, antibiotic use was linked with significantly shorter PFS (median, 1.9 vs 7.4 months; hazard ratio [HR], 3.1; 95% CI, 1.4–6.9; P < .01) and OS (median, 17.3 months vs 30.6 months; HR, 3.5; 95% CI, 1.4–6.9; P < .01).

For patients with NSCLC, there was no significant difference in primary progressive disease among patients who received antibiotics and those who did not. However, there was a significant effect on both PFS (median, 1.9 months vs 3.8 months; HR, 1.5; 95% CI, 1.0–2.2; P = .03) and OS (median, 7.9 months vs 24.6 months; HR, 4.4; 95% CI, 2.67.7; P < .01).

The researchers hypothesized that antibiotics might even have an effect 60 days from start of therapy with immune checkpoint inhibitors. Looking at this timeline, they found that antibiotic use was associated with significantly worse PFS and increased risk for primary progression in patients with RCC. Among patients with NSCLC, antibiotic use 60 days out was significantly associated with worse OS, but not worse objective response or PFS.

“More studies are warranted to confirm the deleterious effect of antibiotic use in large prospective trials and to develop novel diagnostic tools based on gut microbiota in cancer patients, to predict response/resistance to ICIs and identify the key microbiota signatures for each tumor site,” the researchers wrote.