ESMO 2022: Longitudinal Analysis Reveals Gut Microbiota Shift During Standard Therapies in Metastatic Renal Cell Carcinoma (mRCC)

(UroToday.com) During the second Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers, Dr. Alves Costa Silva presented a longitudinal assessment of gut microbiota during treatment for metastatic renal cell carcinoma (mRCC). It has previously been noted that the baseline gut microbiota composition is associated with outcomes for patients receiving immune-checkpoint blockade for mRCC.


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However, an assessment of changes in gut microbiota during the course of mRCC therapies has not, to date, been described.

To assess this, the authors prospectively collected fecal samples of all patients with mRCC who started a 1st or >2nd line treatment with ICB or TKI or combinations under a protocol at Gustave Roussy (NCT04567446). Fecal samples were collected before and during treatment (within 1, 3, 6 and 12 months of treatment start).

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Shot gun metagenomic sequencing (MGS) data was performed using multivariate and pair-wise/fold ratio. Patients treated with TKI were classified as either responders (R) (CR+PR+SD and OS>12 months) or non-responders (NR) (PD and OS<12 months). Patients treated with ICB were classified as elite if CR+PR with PFS>12 months and OS>24 months by RECIST1.1.

Between February 2016 and July 2021, the authors screened 160 patients with mRCC for enrollment of whom 127 met inclusion criteria. Among patients treated with TKI, ORR was 48% and more than a half experienced related diarrhea. For patients treated with ICB, ORR was 31%.

Overall, the authors observed significant differences in alpha and beta diversity of gut microbiota between IMDC risk groups with intermediate IMDC harboring immunogenic commensals (Faecalibacterium, Akkermansia spp, Ruminococcaceae).

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Additionally, they found differences between responders and non-responders among those treated with TKI: non-responders were more likely to harbor pro-TH17 bacteria such as Veillonella parvula.

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Interestingly, both ICB and TKI induced significant and opposite changes in gut microbiota during treatment.

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Among those treated with TKI, there was an increase in pro-Treg tolerogenic bacteria (belonging to Enterocloster genus or diarrhea-associated B. intestinalis and Klebsiella), at the expense of health-related Eubacteriaceae and Bifidobacteria in resistant patients. In contrast, among those treated with ICB, there was a loss of tolerogenic Enterocloster gen. in patients with an elite response and the loss of health-related bacteria in non-responders.

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The authors, therefore, conclude that, in contrast to ICB, treatment with TKI for mRCC favors the over-representation of harmful commensals despite treatment success.

Presented by: Carolina Alves Costa Silva, PhD Student, Gustave Roussy Institute, Villejuif, France


Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 European Society for Medical Oncology (ESMO) Annual Congress, 9-13 September 2022.