Antibiotics may negatively impact immunotherapy outcomes

February 21, 2017

Administration of broad-spectrum antibiotics in patients with metastatic renal cell carcinoma (RCC) undergoing treatment with immune checkpoint inhibitors may have a negative effect on the efficacy of the immunotherapy drugs, according to the results of a recent retrospective analysis.

Administration of broad-spectrum antibiotics in patients with metastatic renal cell carcinoma (RCC) undergoing treatment with immune checkpoint inhibitors may have a negative effect on the efficacy of the immunotherapy drugs, according to the results of a retrospective analysis presented at a press conference ahead of the Genitourinary Cancers Symposium in Orlando, FL.

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“This is the first analysis evaluating the impact of broad spectrum antibiotics on outcomes in metastatic renal cell carcinoma patients treated in the era of immune checkpoint inhibitors,” study co-author Lisa Derosa, MD, of the Gustave Roussy Cancer Institute, Paris-Sud, University in Villejuif, France, said during the press conference. “Recent use of broad spectrum antibiotics prior to immune checkpoint inhibitors negatively influences outcomes even after adjustment for prognostic risk factors.”

It is known that the use of antibiotics alters the gut microbiota composition and decreases bacterial diversity within the body. According to Dr. Derosa, new evidence found in animal studies suggested an interrelationship between broad spectrum antibiotics and immune checkpoint blockade in terms of efficacy.

With this study, Dr. Derosa and co-authors sought to evaluate whether antibiotics affected the efficacy of immune checkpoint blockade used in the treatment of metastatic RCC. The authors enrolled 80 patients who were treated with anti-PD-1/PD-L1 monotherapy or combination treatments. Patients were classified as being antibiotics positive (20%; antibiotics up to 1 months prior to first treatment) or antibiotics negative.

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Patients who received antibiotics had a significantly decreased progression-free survival compared with patients who were antibiotics negative (2.3 vs. 8.1 months; p<.001). Additionally, when looking at patients treated only with nivolumab (Opdivo), those patients who received antibiotics had a significantly decreased progression-free survival compared with patients who were antibiotic negative (p<.009). The authors said this difference remained even after adjusting the data for age, gender, risk group, tumor burden, and proton pump inhibitor use.

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According to Dr. Derosa, there are also preliminary data indicating that overall survival may also be shorter in patients who had received antibiotics, but longer follow-up is still needed.

“Last year, we saw some fascinating articles published in the journal Science which suggested that immune-based therapies for cancer may have a complex interplay with the host’s microbiome,” said press conference moderator Sumanta Pal, MD, of City of Hope, Duarte, CA.

“Specifically, these studies showed that based on the bacterial composition of the gut one could have an impact on the effectiveness of checkpoint inhibitors, including PD-1 inhibitors and CTLA-4 inhibitors, which are used for melanoma and a variety of other diseases. Dr. Derosa’s data is compelling and may indirectly support this evidence, which to date has been in mice.”

Several of Dr. Derosa’s co-authors have a financial or other relationship with Bristol-Myers Squibb and/or other pharmaceutical companies.

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