Do Antibiotics Impair Efficacy of Immunotherapy in Kidney Cancer?

Antibiotics administered less than a month before initiation of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) immune checkpoint blockade therapy with or without cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitors for patients with advanced kidney cancer might impair tumor control, according to authors of a retrospective analysis that will be presented at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held February 16–18 in Orlando, Florida (abstract 462).

“Recent use of antibiotics prior to immune checkpoint inhibitor therapy negatively influences outcomes even after adjustment for prognostic risk factors,” noted lead study author Lisa Derosa, MD, of the Gustave Roussy Cancer Institute, Paris-Sud University in Villejuif, France. “These early findings show that doctors prescribing cancer immunotherapy should pay closer attention to antibiotic use.”

The findings might be due to specific gut microbiota. Prior research had suggested that in mice, gut bacteria can interact with immune system cells in a manner that can improve immune checkpoint inhibition’s antitumor efficacy.

The new analysis included 80 patients diagnosed with metastatic renal cell carcinoma (mRCC) who had participated in prospective clinical trials of PD-1 or PD-L1 inhibitors or combination treatments of PD-1 and CTLA-4 inhibitors or PD-L1 inhibition plus bevacizumab. Most patients (88%) had clear-cell mRCC histology. Of the 80 patients, 16 (20%) had been administered broad-spectrum antibiotic agents up to a month prior to initiation of cancer immunotherapy.

Tumors progressed more rapidly among patients who had been administered antibiotics than in those who had not. Objective response rate (ORR) was lower among patients who had received antibiotics (P < .002).

Median progression-free survival was 2.3 months and 8.1 months for the two groups (P < .001). That statistical association survived multivariate adjustments for patient age, gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk category, tumor burden, and proton-pump inhibitor status. There was a trend toward a similarly negative association between antibiotics use and overall survival among patients receiving immune checkpoint blockade therapy but it was too soon for any definitive conclusion about that outcome, Derosa cautioned.

The study authors are now investigating the biological mechanisms underlying the association but noted that further studies are needed to better understand how alteration of gut microbiota affects immunotherapy outcomes. It is not yet clear whether the findings have implications for other cancer types but antibiotics are frequently administered to patients with cancer as prophylaxis against infection, Derosa noted.

“As cancer immunotherapy options grow and evolve, we’re beginning to understand more about the relationship between gut bacteria and the immune response to cancer,” noted ASCO Expert Sumanta Pal, MD, of City of Hope in Duarte, California. “It’s remarkable that antibiotic use could have such a negative impact on the efficacy of immunotherapy. This study suggests that patient antibiotic use should be considered carefully so that the possible benefits of immunotherapy are not compromised.”