Prospective manipulation of the gut microbiome with microbial ecosystem therapeutic 4 (MET4) in HPV-related locoregionally-advanced oropharyngeal cancer squamous cell carcinoma (LA-OPSCC) undergoing primary chemoradiation: ROMA2 study.

Autor: Oliva M; Department of Medical Oncology, Catalan Institute of Oncology, Barcelona, Spain.; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Heirali A; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada., Watson G; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Rooney AM; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada., Cochrane K; Nubiyota LLP, Guelph, ON, Canada., Jennings S; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Taylor R; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Xu M; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Hosni A; Department of Radiation Oncology, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Hope A; Department of Radiation Oncology, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Bratman SV; Department of Radiation Oncology, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Chepeha D; Department of Otolaryngology- Head & Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada., Weinreb I; Department of Pathology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada., Perez-Ordonez B; Department of Pathology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada., Nin RM; Department of Medical Oncology, Catalan Institute of Oncology, Barcelona, Spain., Waldron J; Department of Radiation Oncology, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Xu W; Biostatistics Department, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Hansen AR; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Siu LL; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Coburn B; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. bryan.coburn@uhn.ca.; Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, ON, Canada. bryan.coburn@uhn.ca., Spreafico A; Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. anna.spreafico@uhn.ca.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2024 Jun; Vol. 130 (12), pp. 1936-1942. Date of Electronic Publication: 2024 May 07.
DOI: 10.1038/s41416-024-02701-y
Abstrakt: Background: Gut microbiome modulation to boost antitumor immune responses is under investigation.
Methods: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis.
Results: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics.
Conclusions: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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