Antibiotic therapy 30 days prior to the initiation of immunotherapy is associated with reduced response rate, progression-free survival and overall survival in women with recurrent gynecologic cancers, according to a new study from Cleveland Clinic.
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“Understanding factors that may contribute to immunotherapy resistance is essential to improving survival for our patients,” says Cleveland Clinic’s Laura Chambers, DO, first author on the study. “Studies in patients with non-gynecologic cancers, such as melanoma and non-small cell lung carcinomas, have demonstrated that antibiotics prior to immunotherapy may negatively affect treatment outcomes. We sought to understand how this would impact women with gynecologic cancer.”
In a retrospective study recently published in Gynecologic Oncology, Drs. Chambers and Vargas looked at 101 women with recurrent endometrial cancer, cervical cancer or ovarian cancer who received immunotherapy between January 2017 and September 2020. Of that group, 58 women (56.9%) received antibiotics, with 23 (22.8%) receiving antibiotics within the 30 days prior to immunotherapy treatment and 47 (46.5%) receiving antibiotics concurrently with their immunotherapy.
Patients received antibiotic treatment for a variety of reasons, including urinary tract infection, upper respiratory tract infection or pneumonia, gastrointestinal/pelvic abscess, skin/port infection, neutropenic prophylaxis or C. difficile colitis. There were no differences in indications for antibiotics between the groups.
Overall, researchers found that antibiotics prior to immunotherapy were associated with a significant reduction in progression-free and overall survival in women with three different recurrent gynecologic cancers: endometrial, cervical and ovarian cancer. Furthermore, antibiotics prior to immunotherapy were also associated with a significantly decreased immunotherapy response, compared with patients who did not receive antibiotics or only received them during their immunotherapy.
Patients who received antibiotics within 30 days of immunotherapy had a shorter progression free survival of 2.9 months, compared with those who had concurrent antibiotics and no antibiotics, with progression free survival of 8.9 months. In terms of overall survival, patients who had antibiotics prior to immunotherapy lived 9.3 months compared with 19.9 months for those that had concurrent antibiotics and no antibiotics.
“We found that antibiotic use timing was a significant factor – with use prior to immunotherapy associated with a survival difference of approximately 10 months,” adds senior author Roberto Vargas, MD, clinical assistant professor at the Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, and associate staff in Gynecologic Oncology at Cleveland Clinic. “Further prospective study is needed to understand the mechanism through which the timing of antibiotic therapy impacts outcomes, particularly the impact on the gut and intra-tumoral microbiome.”
Previous research has demonstrated that antibiotic treatment is a negative predictor of response to immunotherapy and overall survival in patients with melanoma, non-small cell lung cancer, bladder cancer and renal cell carcinoma. Its effects on response rates, progression and outcomes in patients with gynecologic cancer had not been elucidated until now. Studies in non-gynecologic cancers have demonstrated the gut microbiome is one mechanism through which antibiotics may impact oncologic outcomes.
Although this is still a hypothesis, the research team believes that response to immunotherapy may be impacted in part by the gut microbiota, which may be altered by antibiotic therapy. Dr. Chambers notes “over the last decade, there has been an increasing focus on the gut microbiome as a mediator in health and disease states, such as cancer,” Dr. Chambers says. “We believe that the gut microbiome may act as a mediator for certain types of cancer treatments, including immunotherapy. Understanding how antibiotic therapy, and the gut microbiome, impact immunotherapy response and oncologic outcomes may allow for therapeutic intervention and modulation for our gynecologic cancer patients.”