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Use of antibiotics could reduce efficacy of immunotherapy
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Cancer worsened more quickly in patients who received antibiotics less than 1 month before starting immunotherapy, according to a retrospective analysis scheduled for presentation at the Genitourinary Cancers Symposium.
“The use of antibiotics prior to immune checkpoint therapy negatively influences outcome, even after adjusting for prognostic risk factors,” Lisa Derosa, PhD candidate at Institut Gustave Roussy of Université Paris-Sud in Villejuif, France, said during a press conference. “The data that were presented are just preliminary, so we have a lot of work to do. I think the results are really important because of the kind of connections between microbiome, antibiotics and immunotherapy.”
Broad-spectrum antibiotics are commonly prescribed to patients with cancer to prevent or treat infections related to treatments or weakened immune systems. Derosa and colleagues analyzed the impact antibiotics have on patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors.
Researchers enrolled 80 patients (65% men) treated in prospective trials at Gustave Roussy with PD-1/PD-L1 inhibitors alone (n = 67); anti–PD-1 plus CTLA-4 inhibitors (n = 10); or an anti–PD-L1 plus bevacizumab (Avastin, Genentech; n = 3) with available data on antibiotic use.
Of those enrolled, 21% had favorable-risk disease, 57% had intermediate-risk disease and 22% had poor-risk disease. Most patients had clear-cell histology (88%) and had undergone nephrectomy (80%).
Sixteen patients had been treated with antibiotics up to 1 month prior to the first injection of immune checkpoint inhibitors, mostly receiving beta-lactamases and fluoroquinolones.
Endpoints of the study included PFS, objective response rate and OS.
Median follow-up was less than 6 months.
Patients with mRCC who had received antibiotics had a shorter PFS compared with those not given antibiotics (2.3 months vs. 8.1 months; P < .001). This association persisted in analyses adjusted for variables, such as patient age, gender and tumor characteristics.
ORR also was lower in patients who had received antibiotics (P < .002).
Researchers noted it was too early to report on OS, but they observed a negative trend driven in patients who had received antibiotics prior to immunotherapy.
Research of the microbiome across multiple disease states has been extensive in recent years, including its influence in inflammatory bowel disease and starvation disorders, Sumanta Pal, MD, associate professor of medical oncology at City of Hope Comprehensive Cancer Center, ASCO expert and a HemOnc Today Editorial Board member, said during the press conference.
“Specifically, these studies showed that, based on bacterial composition of the gut, one could have an impact with the effectiveness of checkpoint inhibitors, including PD1 inhibitors and CTLA-4 inhibitors, which are used for melanoma and a variety of other diseases,” Pal said. “Dr. Derosa shows that antibiotic therapy may have a direct impact on how well the PD1 inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) works in patients with kidney cancer, and this could, in turn, impact how effective immune therapy is. There are studies ongoing to do a deeper dive and confirm the mechanisms of action.”
Follow-up studies with additional patients are needed to reach a definitive conclusion on OS. Other studies on the impact of antibiotics on the progression of kidney and lung cancers are ongoing, Derosa said.
Pal and Derosa both stressed that patients on antibiotics and receiving immunotherapy should continue on their antibiotics.
“I would propose these data are very intriguing, but it’s important to keep in mind it was retrospectively generated and, therefore, I would consider it hypothesis generated,” Pal said. “Having said that, the observations Dr. Derosa made have some consistency with preclinical observations. So, with further prospective validation, we may offer some insight as to whether or not bacterial composition of the gut could affect clinical outcomes, and that might help us guide antibiotic usage. ... I would certainly use antibiotics as medically indicated under these circumstances.” – by Chuck Gormley
Disclosure: Derosa reports no relevant financial disclosures. Please see the abstract for a list of all researchers’ relevant financial disclosures.