New findings from the Princess Margaret Cancer Centre show that taking antibiotics prior to treatment with anticancer drugs known as immune checkpoint inhibitors may have negative effects on an individual’s overall survival.
Immune checkpoint inhibitors work by blocking certain proteins on immune cells. The proteins that are blocked are involved in limiting the activity of the immune system. By blocking these proteins, the checkpoint inhibitor ‘releases the breaks’, enabling immune cells to better target and kill cancer.
Interestingly, studies have shown that the gut microbiome—i.e., bacteria, fungi and viruses that live in the digestive tract—can alter the effectiveness of immune checkpoint inhibitors.
“Given that antibiotics impact the gut microbiome, we were interested in testing whether taking antibiotics before immune checkpoint inhibitor treatment affected outcomes,” says Dr. Lawson Eng, a Clinician Investigator at the Princess Margaret Cancer Centre and lead author of the study. “Until now, studies looking at this issue have been limited in size and consistency.”
To address this, the team analyzed data from a large population cohort. The cohort comprised over 2,700 adults aged 65 or older with cancer who received immune checkpoint inhibitor therapy in Ontario between 2012 and 2018.
Using advanced statistical approaches, the team discovered that antibiotic exposure within one year prior to immune checkpoint inhibitor treatment was associated with worse overall survival.
This effect was most pronounced with exposure to fluoroquinolones—a group of antibiotics commonly used to treat respiratory and urinary tract infections. Exposure to fluoroquinolone increased the risk of mortality in this population by up to 65%.
“While antibiotics are commonly prescribed for various conditions, our study highlights the importance of considering exposure to antibiotics before treatment with immune checkpoint inhibitors,” explains Dr. Eng. “More research is needed to determine whether interventions could be developed to restore the gut microbiome and counteract the negative effects that we identified,” explains Dr. Eng.
This work was supported by ICES, the Ontario Ministry of Health and the Ministry of Long-Term Care, the ASCO/Conquer Cancer Foundation and The Princess Margaret Cancer Foundation.
Dr. Liu receives honoraria from Pfizer, Novartis, Merck, AstraZeneca, Takeda, AbbVie, Bayer, Bristol Myers Squibb, Roche Canada, Jazz Pharmaceuticals and Amgen; is a consultant for Pfizer, Novartis, AstraZeneca/MedImmune, Takeda and Roche Canada; and receives research funding from Roche, AstraZeneca/MedImmune, Takeda, Boehringer Ingelheim. Dr. Peppercorn is employed by and owns stock from GlaxoSmithKline; is a consultant for Abbott Laboratories; and receives research funding from Outcomes4Me. Dr. Bedard is a consultant for BMS, Pfizer, Seattle Genetics, Lilly, Amgen, Merck and Gilead Sciences; and receives research funding from Bristol Myers Squibb, Sanofi, AstraZeneca, Genentech/Roche, GlaxoSmithKline, Novartis, Nektar, Merck, Seattle Genetics, Immunomedics, Lilly, Amgen, Bicara Therapeutics and Zymeworks. Dr. Krzyzanowska is a consultant for Eisai, Lilly, Ipsen and Bayer; and receives research funding from Eisai, Exelixis and Lilly.
Eng L, Sutradhar R, Niu Y, Liu N, Liu Y, Kaliwal Y, Powis ML, Liu G, Peppercorn JM, Bedard PL, Krzyzanowska MK. Impact of Antibiotic Exposure Before Immune Checkpoint Inhibitor Treatment on Overall Survival in Older Adults With Cancer: A Population-Based Study. J Clin Oncol. 2023 Feb 24:JCO2200074. doi: 10.1200/JCO.22.00074.
Immune checkpoint inhibitors are one type of cancer immunotherapy that have been effective in treating a number of solid tumours, including those of the skin, lung, colon, head and neck, and genitourinary tract.