In this study, Dr. Derosa and colleagues prospectively collected stool on 65 patients from the NIVOREN study5. NIVOREN is a multicenter, open-label, non-controlled, phase II safety study in patients with metastatic renal cell carcinoma and who have progressed during or after one prior systemic anti-angiogenic treatment. Patients were classified as primary resistant or non-primary resistant based on RECIST criteria and the metagenomic data from their stool was compared between the two different cohorts.
Of the 65 patients, 27 (39%) were classified as being resistant to nivolumab, and 42 (61%) were not resistant, based on best response. The microbiome diversity was not significantly different among the two cohorts of patients. After excluding antibiotic treated patients, Akkermansia muciniphila and Bacteroides salyersiae were more abundant in patients sensitive to nivolumab than those resistant to nivolumab. The investigators then performed fecal microbiota transplant (FMT) in immune-checkpoint inhibitor resistant RENCA mice (murine renal cell carcinoma model) and found that Akkermansia muciniphila and Bacteroides salyersiae could restore the efficacy of immune checkpoint inhibitors in a subpopulation of FMT recipients.
Prior studies have implicated Akkermansia muciniphila in various autoimmune conditions including psoriasis and type I diabetes6,7. They have also shown that coloniziation of Akkermansia muciniphila in mouse models may lead to expression of genes involved in the regulation of the immune response8. Cecal colonization by A. muciniphila resulted in up-regulation of genes involved in antigen presentation.
Oral gut microbe cocktails, also known as “crapsules” are in development for a variety of diseases including inflammatory bowel disease and clostridium difficile9,10. It will be interesting the follow the story of the gut microbiome and its influence of cancer therapy – perhaps “crapsules” will be used in the sequence of various cancers, either prior to therapy to prime the immune system or in conjunction to maximize the effect.
During the poster discussion session by Dr. Brian Shuch, he noted that this was the largest prospective analysis which supports the hypothesis that the gut microbiome predicts outcome to nivolumab for patients with RCC and that two future questions to consider are whether or not we should be modulating the microbiome prior to or after therapy and if we should closely regulate antibiotics, life style, and diet while on therapy.
Presented By: Brian Shuch, MD
Poster By: Lisa Derosa, MD, Institut de Cancérologie Gustave Roussy, Villejuif IGR
Written by: Jason Zhu, MD Fellow, Division of Hematology and Oncology Duke University Medical Center, Twitter: @TheRealdJasonZhu at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
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