Use of Antibiotics May Adversely Affect Response to Immunotherapy

TON - May 2017, Vol 10, No 3 - Adverse Effects

Orlando, FL—The results of a new study presented at the 2017 Genitourinary Cancers Symposium suggest that recent use of antibiotics may compromise the efficacy of immunotherapy. The study was conducted in patients with metastatic kidney cancer, but the findings, if proved, may apply to any patient with cancer receiving immunotherapy.

Key findings from the study by Lisa Derosa, MD, a PhD candidate, Gustave Roussy Cancer Institute, Paris-Sud University, Villejuif, France, showed that cancer progressed more rapidly in patients who received antibiotics within 1 month before receiving immunotherapy than in those who did not, and that response rates were lower in antibiotic users compared with nonusers.

Dr Derosa and colleagues stated that this is the first study analyzing the impact of antibiotics on immune checkpoint inhibitors, and the first evidence of a relationship between the gut microbiome and patients’ response to immunotherapy.

Dr Derosa and colleagues’ hypothesis that antibiotics wipe out “good bacteria” in the gut is based on preclinical studies showing that certain microorganisms in the gut interact with the immune system so as to facilitate the effect of immune checkpoint inhibitors.

They conducted a retrospective analysis of 80 patients with metastatic renal-cell carcinoma enrolled in prospective clinical trials of immune checkpoint inhibitors (anti–PD-1/PD-L1 therapy as monotherapy or combined with CTLA-4 or bevacizumab). Sixteen (20%) patients enrolled in the trial were treated with broad-spectrum antibiotics, mostly beta-lactamases and fluoroquinolones, within 1 month of starting treatment with immune checkpoint inhibitors.

Patients who received antibiotics before starting immunotherapy had significantly greater disease progression compared with those who did not; median progression-free survival was 2.3 months in those who received antibiotics versus 8.1 months in those who did not (P <.001).

In addition to significantly worse progression-free survival rates, overall response rates to checkpoint inhibitors were also lower among antibiotic users, said lead investigor Dr Derosa.

“Although it’s too early to conclude about overall survival, with median follow-up of <6 months, there is already a negative trend in the antibiotic-positive group,” she added.

Dr Derosa suggested that the findings may be applicable to other tumor types, because antibiotics are frequently used in patients with cancer to prevent and manage treatment-related infections. At this time, she does not recommend withholding antibiotics from patients taking checkpoint inhibitors, noting that the data are preliminary. Further studies are needed to confirm the study’s hypothesis, and to better understand the relationship between alterations to the gut microbiome and the use of immunotherapy.

Sumanta Pal, MD, Co-Director, City of Hope Kidney Cancer Program, Duarte, CA, and moderator of a press cast where these findings were presented, agreed.

“While Dr Derosa’s findings are very intriguing, they were retrospectively generated, and therefore are hypothesis-generating. Having said that, the observations are consistent with preclinical observations. With further prospective validation, we may gain insight as to whether the bacterial composition of the gut affects clinical outcomes, and this could help guide us in our antibiotic usage. Meanwhile, we must consider that antibiotics are used under circumstances that are medically necessary,” Dr Pal said.

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Last modified: June 8, 2017