A new retrospective analysis suggests that immunotherapy may be less effective in patients who receive antibiotics less than a month before starting treatment. In the study, cancer worsened more quickly in such patients than in those who did not receive antibiotics (median progression-free survival 2.3 months vs. 8.1 months). The study was presented at ASCO's 2017 Genitourinary Cancers Symposium in Orlando.

According to the authors, this study is the first to analyze the impact of antibiotics on immune checkpoint inhibitors and provides the first evidence of a relationship between the gut microbiome and patients' response to immunotherapy.

The researchers believe that the negative effect of antibiotics is due to the antibiotics wiping out the "good bacteria" in the gut. Earlier, research in mice suggested that certain microorganisms dwelling in the gut interact with the immune system in a way that seems to help immune checkpoint inhibitors work better.

"These early findings show that doctors prescribing cancer immunotherapy should pay closer attention to antibiotic use," said lead study author Lisa Derosa, MD, a PhD candidate at the Gustave Roussy Cancer Institute, Paris-Sud University in Villejuif, France. "This research may be relevant to more than just kidney cancers, as antibiotics are commonly prescribed to patients with cancer to prevent or treat infections related to cancer treatment or weakened immune system."

The analysis included 80 patients with metastatic renal cell carcinoma who were enrolled in prospective clinical trials of immune checkpoint inhibitors. The patients were treated with single-agent PD-1 or PD-L1 inhibitors, combinations of PD-1 inhibitors and CTLA-4 inhibitor or combinations of PD-L1 inhibitor and bevacizumab. Overall, 16 patients had been treated with broad-spectrum antibiotics up to one month before receiving the first dose of immunotherapy.  

Cancer worsened faster in patients who had received antibiotics, regardless of factors such as patient age, gender and tumor characteristics. According to the authors, there is preliminary indication that overall survival may also be shorter with antibiotic use, but longer follow up is needed to reach a definitive conclusion.

"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," said ASCO Expert Sumanta Pal, MD. "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."

The researchers plan to enroll additional patients in this study. At the same time, they will continue studies in mice to try to pinpoint the types of gut bacteria that affect response to immune checkpoint inhibitors and the kinds of antibiotics that have the greatest impact on outcomes. Meanwhile, other ongoing studies in kidney and lung cancers are exploring the connection between antibiotic use and outcomes with cancer immunotherapy.

The rates of kidney cancer have been steadily rising over the last decade. Renal cell carcinoma is the most common type of adult kidney cancer, making up about 85% of diagnoses.

This study was supported by grants from the Philanthropia Foundation.