229P - BISQUIT: A randomized phase II trial of Prebiotics and Probiotics (PreProbiotics) during chemoradiation (CRT) for patients (pts) with squamous cell carcinoma of the anal canal (SCCA)

Background

The intestinal microbiota influences the onset of colorectal cancer and replacement of "carcinogenic" bacteria by a protective microbiota has motivated research with PreProbiotics. Yet, there are no such studies in SCCA.

Methods

Randomized open label phase II trial (NCT03870607) of PreProbiotics administered during CRT in pts with ≥ T2N0M0 SCCA. Pts candidates for CRT were randomized to receive or not PreProbiotics (Symbioflora^â- Lactobacillus sp, Bifidobacterium lactis, fructooligosaccharide) starting one week prior to and during CRT until 8 weeks post therapy. Pts on antibiotics were excluded. The primary endpoint was cCR at 8 weeks post CRT. Secondary endpoints were cCR at 6 months, metabolic response by 18-FDG PET at 8 weeks, tolerability (completion of CRT < 7 weeks), circulating HPV (cHPV; RT-PCR) kinetics and changes in fecal microbiota (16S rRNA gene sequencing). Planned sample size was 75 pts. We present interim analyses.

Results

From May/2019 to Dec/2022, 34 pts were enrolled: 79% were female, 2 were HIV positive, 73.5% had stage III; 83.3% of tumors tested positive for HPV DNA; 32 pts received platin-fluoropyrimidine CRT and 31, IMRT. Groups were similar at baseline according to age, stage, ECOG, radiation (RT) dose. At 8 weeks, the rates of cCR in the Control vs PreProbiotics groups were 83.3% vs 62.5% (p = 0.16) and of complete metabolic response, 87% vs 67% (p = 0.19); at 6 months, cCR rates were 88.8% and 87.5%, respectively. In Control vs PreProbiotics groups, there were no differences in rates of G3/4 toxicities (72.2% vs 62.5%; p = 0.54) or rates of ≥ 7 weeks to complete CRT (16.6% vs 18%; p = 0.10). We did not identify differently abundant bacteria genus with the use of PreProbiotics (lack of engraftment) or between groups post CRT (Wilcoxon, all p > 0.05). We did not identify patterns of fecal bacteria predictive of G3/4 toxicities or tolerability to CRT in each study group. Kinetics of HPV cDNA analysis will be shown.

Conclusions

The use of PreProbiotics during CRT for localized SCCA did not affect cCR rates, tolerability, or fecal microbiota.

Clinical trial identification

NCT03870607.

Legal entity responsible for the study

The authors.

Funding

AC Camargo Cancer Center.

Disclosure

All authors have declared no conflicts of interest.