학술논문
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
Document Type
Original Paper
Author
Oliva, Marc; Heirali, Alya; Watson, Geoffrey; Rooney, Ashley M.; Cochrane, Kyla; Jennings, Sarah; Taylor, Rachel; Xu, Minge; Hosni, Ali; Hope, Andrew; Bratman, Scott V.; Chepeha, Douglas; Weinreb, Ilan; Perez-Ordonez, Bayardo; Nin, Ricard Mesia; Waldron, John; Xu, Wei; Hansen, Aaron R.; Siu, Lillian L.; Coburn, Bryan; Spreafico, Anna
Source
British Journal of Cancer. 130(12):1936-1942
Subject
Language
English
ISSN
0007-0920
1532-1827
1532-1827
Abstract
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.