Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma

Gianluca Ianiro,Luca Masucci,Maurizio Sanguinetti,Ernesto Rossi,Loris Riccardo Lopetuso,Federica Armanini,Roberto Iacovelli,Giovanni Schinzari,Antonio Gasbarrini,Andrew M Thomas,Carlo Romano Settanni,Nicola Segata,Aitor Blanco-Miguez,Clarissa Consolandi,Giovanni Cammarota,Giampaolo Tortora,Gianluca Quaranta,Francesco Asnicar

doi:10.1038/s41467-020-18127-y

Abstract

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea.

Highlights

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date
Donor faecal microbiota transplantation (FMT) is more effective than placebo FMT in treating tyrosine kinase inhibitors (TKI)-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces
Nineteen patients presented with a G2 diarrhoea, and one with a G3 diarrhoea, according to the Common Terminology Criteria (CTC) for Adverse Events (AE) version 4.020

Summary

Introduction

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. We report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea. The therapeutic modulation of gut microbiota could alleviate TKI-induced diarrhoea, and probiotics have been suggested as a possible treatment option for this condition, but little evidence supports this indication[12,13]. We report findings from a randomised clinical trial of donor FMT versus placebo FMT to treat diarrhoea induced by TKI in patients with metastatic renal cell carcinoma (NCT04040712). Our findings suggest that the therapeutic manipulation of gut microbiota may become a treatment option to manage TKIdependent diarrhoea

Methods

Results

Conclusion