ASCO GU 2017: In Advanced Kidney Cancer, Antibiotic Use Lowers Efficacy of Immunotherapy
ALEXANDRIA, Va. – 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 will be presented at the upcoming 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 (microbes residing in the gut) 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 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 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 (antibiotics that work against a wide range of bacteria) up to one month before receiving the first dose of immunotherapy.
Key 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 preliminary indication that overall survival may also be shorter with antibiotic use, but longer follow up is needed to reach a definitive conclusion.
Next Steps
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.
About Kidney Cancer
An estimated 64,000 people will be diagnosed with kidney cancer in 2017 in the United States, and more than 14,400 will die of the disease.1 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.
1 Cancer Facts & Figures 2017, American Cancer Society, 2017.
2017 Genitourinary Cancers Symposium: Presentation Information
Poster Session C
Saturday, February 18, 2017: 7:00 AM – 7:55 AM EST
Saturday, February 18, 2017: 11:30 AM – 1:00 PM EST
Rosen, Gatlin Ballroom B, Level 1
Lisa Derosa, MD
Gustave Roussy Cancer Campus,
Paris-Sud University
Villejuif, France
Abstract 462: Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors.
Authors: Lisa Derosa, Bertrand Routy, David Enot, Giulia Baciarello, Christophe Massard, Yohann Loriot, Karim Fizazi, Bernard J. Escudier, Laurence Zitvogel, Laurence Albiges; Department of Cancer Medicine, Gustave Roussy Cancer Campus, Paris-Sud University, Villejuif, France; Institut Gustave Roussy Cancer Centre, Villejuif, France; Gustave Roussy, University of Paris Sud, Villejuif, France; Institut Gustave Roussy, Villejuif, France
Background: Preclinical data demonstrated that microbiota modulates activity of immune checkpoint inhibitors (ICB) and broad-spectrum antibiotics (ATB) damper their efficacy. However, the impact of ATB in cancer patients (pts) treated with ICB remains unknown. Our study evaluates the effect of ATB use in metastatic renal cell carcinoma (mRCC) pts treated with ICB. Methods: We conducted a retrospective analysis of mRCC pts treated in prospective trials at Gustave Roussy with PD1/PD-L1 inhibitors alone or in combination. ATB (+)/(-) group were defined as pts treated or not with ATB at baseline (up to 1 month prior to the 1st injection of ICB). Progression-Free survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS) were compared in each group (ATB (+) vs ATB (-)). Statistical analyses were performed using Kaplan-Meier method and Cox regression adjusted for risk factors. Results: We enrolled 80 mRCC pts treated with anti-PD-1/PD-L1 monotherapy (n=67), anti-PD-1 plus CTLA-4 (n=10) or anti-PD-L1 plus bevacizumab (n=3) with available data on ATB. Majority of pts were male (65%), clear-cell histology (88%), and had prior nephrectomy (80%). With regard to IMDC risk groups, 21%, 57%, and 22% had favorable, intermediate, and poor-risk disease, respectively. Sixteen (20%) pts belonged to the ATB (+) group (mostly receiving beta-lactamases and fluoroquinolones). ATB (+) had decreased PFS compared to ATB (-), 2.3 vs. 8.1 months, p<0.001. This statistical association was maintained after multivariate analysis adjusted for age, gender, IMDC risk groups, tumour burden and proton pomp inhibitors. In addition, ORR was lower in ATB (+) compared with ATB (-) (p<0.002). Even though it is too early to conclude on OS (median follow-up <6 months), there was already a negative trend driven in ATB (+). Conclusions: This is the first analysis evaluating the impact of ATB in mRCC pts treated in the era of ICB. Recent use of ATB prior to ICB, negatively influences responses even after multivariable analysis for prognostic risk factors. Further studies are warranted to investigate whether the alteration of gut microbiota compositions is responsible for this different outcome.
2017 Gastrointestinal Cancers Symposium News Planning Team Sumanta K. Pal, MD, American Society of Clinical Oncology (ASCO); Daniel A. Hamstra, MD, PhD, American Society for Radiation Oncology (ASTRO); and Marc Dall’Era, MD, Society of Surgical Oncology (SSO)
About the American Society for Radiation Oncology:
The American Society for Radiation Oncology (ASTRO) is the premier radiation oncology society in the world, with more than 10,000 members who are physicians, nurses, biologist, physicists, radiation therapists, dosimetrists and other health care professionals that specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, the Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology, Biology, Physics, Practical Radiation Oncology, and Advances in Radiation Oncology, developed and maintains an extensive patient website; and created the Radiation Oncology Institute, a non-profit foundation to support research and education efforts around the world that enhance and confirm the critical role of radiation therapy in improving cancer treatment. Learn more about ASTRO.
About the American Society of Clinical Oncology:
Founded in 1964, the American Society of Clinical Oncology, Inc. (ASCO®) is committed to making a world of difference in cancer care. As the world’s leading organization of its kind, ASCO represents more than 40,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of the highest-quality patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation. Learn more at www.ASCO.org, explore patient education resources at www.Cancer.Net, and follow us on Facebook, Twitter, LinkedIn, and YouTube.
About the Society of Urologic Oncology:
The Society of Urologic Oncology (SUO) was created in 1984 to enable qualified members primarily interested in the care of patients with malignant genitourinary diseases to meet for the purpose of discussion, development, and implementation of ideas to improve care. The Society and its bylaws conform to the guidelines and bylaws of the American Urological Association (AUA). The purpose of the SUO is to develop educational and research initiatives and to study issues in urologic oncology and provide physician statements that represent a state of the art assessment of these issues to other organizations. The Society also provides a forum for identifying the urologic oncologist as a physician with specific expertise in the study and treatment of genitourinary malignancies. In recognition of the multidisciplinary efforts involved in the study and treatment of genitourinary malignancies, the Society seeks to incorporate multiple disciplines in achieving these goals. The Society supports the activities of multiple disciplines in the common objectives of seeking an increased understanding and successful treatment of genitourinary malignancies. The SUO seeks to improve the care of patients with malignant urologic disease and to provide a forum for the discussion of problems relating to malignant urologic disease. Our objectives include: 1) Stimulating research in and the teaching of urologic oncology, 2) Disseminating the principles of urologic oncology to the medical profession at large, 3) Bringing urologists into a Society whose work is entirely, or principally with malignant disease, 4) Being identified as the most qualified organization on matters relating to urologic oncology, and 5) Standardize fellowship training in urologic oncology.