863P - Microbiota and cytokines profile in patients (pts) affected by recurrent metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs) +/- chemotherapy (CT) and prebiotic inulin in the PRINCESS study

Background

ICIs +/- CT have positive but marginal clinical effects in R/M HNSCC. Gut microbiota (GM) modulation might improve activity of ICIs. Inulin, a mixture of polymers of fructosyl units, may modify GM.

Methods

PRINCESS study explores longitudinal changes of GM and circulating cytokines in R/M HNSCC pts treated with ICIs +/- CT plus inulin. Pts receive oral inulin (10 g daily) and ICIs (nivolumab 240 q14 or pembrolizumab 200 q21 +/- CT). Stools and blood samples are collected at scheduled time points (TPs): baseline (T0) and at each radiological assessment (T1-4) until progression. Species-level genome bins (SGB) estimation of taxonomic composition of each stool sample was carried out. Differences in GM of same patients among TPs were explored. 18 cytokines (IL-2, IL-12, CXCL-10, CCL-2, TNF-α, IFN-γ, IL-4, IL-5, IL-10, IL-13, CCL-22, CCL4, IL-6, IL-8, TGF-β, VEGF, IL-21, and IL-15) were measured in plasma at each TPs.

Results

Between November 2021 and April 2023 16 pts have been evaluated. 9 pts had progression-free survival (PFS) > 6 months. No difference in microbial complexity of pts among TPs was found. Samples were not separated according to TPs (p=0.21) while they were segregated by patient. We identified few microbial species (SGBs) differentially abundant between T0 and T1: S. salivarius SGB8007, Roseburia SGB4938, Dorea SGB4571 being increased in T0, while A. shahii SGB2295, I. butyriciproducens SGB15126, B. wadsworthia SGB15452, D. welbionis SGB15078, F. plautii SGB15132, B. caccae SGB1877, B. uniformis SGB1836 were significantly increased in T1. B. uniformis SGB1836 increased in T2 with respect to T0. At T1 progressed (P) pts showed increase of IL-5 and IL-10 (p=0.03) while IL-12 increased in non-P pts (p=0.01). P pts had higher values of IL-6, IL-8, CCL2, and VEGF (p<0.05) at T1.

Conclusions

With the limits of a small population, we found preliminary longitudinal differences in pts GM composition and cytokines Th2 vs Th1 pattern during ICIs +/- CT plus inulin. No safety signals were recorded. Due to our preliminary results, pts accrual will be enlarged to generate more solid data.

Clinical trial identification

NCT0582175 (April 20, 2023).

Editorial acknowledgement

Legal entity responsible for the study

Danilo Galizia.

Funding

Fondazione piemontese per la ricerca sul cancro.

Disclosure

D. Galizia: Financial Interests, Personal, Financially compensated role, medical lessons: MSD; Financial Interests, Personal, Funding, congress coverage: AZ; Financial Interests, Personal, Invited Speaker: Lilly. All other authors have declared no conflicts of interest.