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2017 GU Cancers Symposium: In Advanced Kidney Cancer, Antibiotic Use Lowers Efficacy of Immunotherapy

Key Points

  • 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.
  • 16 of 80 patients had been treated with broad-spectrum antibiotics up to 1 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. 

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 (with median progression-free survivals of 2.3 vs 8.1 months, respectively). The study will be presented by Derosa et al at the upcoming 2017 Genitourinary Cancers Symposium in Orlando, Florida (Abstract 462).

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 a weakened immune system.”

The Study

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 programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, combinations of PD-1 inhibitors and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) inhibitor, or combinations of a PD-L1 inhibitor and bevacizumab (Avastin). Overall, 16 patients had been treated with broad-spectrum antibiotics up to 1 month before receiving the first dose of immunotherapy.

Major Findings

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 a preliminary indication that overall survival may also be shorter with antibiotic use, but longer follow-up is needed to reach a definitive conclusion.

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.

“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.”

This study was supported by grants from the Philanthropia Foundation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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