Association of baseline microbiome and responders to immunotherapy for biochemically recurrent prostate cancer (BCR) without androgen deprivation therapy (ADT).

Abstract

e17111 Background: Patients (pts) with BCR have a rising PSA after definitive therapy but negative CT/Tc99 scans. While there is substantial interest in understanding the gut microbiome in prostate cancer, it remains unclear how it could inform care or how it is associated with responses to treatment. There are no published data on the gut microbiome in BCR where patients are not impacted by androgen deprivation therapy (ADT). Methods: This study (NCT03315871) enrolled pts with intermediate-risk BCR (PSA doubling time (PSADT) of 5-15 months). Treatment was 2 pox viral-based therapeutic cancer vaccines targeting PSA and MUC1/CEA respectively for 7 months. PSA declines were noted based on multiple confirmed PSA declines from an intra-study apex PSA (ISAP; Madan ASCO GU 2018). Shotgun metagenomics sequencing analyses of stool were done in willing pts at baseline and after 4 and 7 months of treatment to study their gut microbiome. Serial PSA and PSMA-tumor volume (PSMA-TV) were also evaluated to define responses. Results: 23 pts were treated/evaluable for response. Baseline medians include age of 69.5 years (58-84), PSA of 5.1 ng/ml (0.9-32.9) and PSA of DT 8.1 months (5-14.4). 18 pts had sequential stool microbiome analysis performed. Nine of 23 (35%) evaluable pts had confirmed ISAP PSA declines after treatment, lasting a median of 140 days (56-375), including delayed responses. 9 pts had declines in PSMA-TV on PSMA PET, including 5 pts with PSA declines and 4 others with PSA stabilization. 18 pts provided stool samples for microbiome analysis, including all 9 pts with PSA responses. As per the alpha diversity metrics (Mann-Whitney U test, p < 0.05), patients with PSA responses had fewer low-abundance microbes at the Pre and Mid timepoints, and by the Post timepoint their microbiomes were dominated by just a few taxa. Beta diversity analysis using Bray-Curtis distances showed that PSA responders and non-responders had distinct microbiome composition at all three time points (PERMANOVA p < 0.05), with no differences over time within either group. Conclusions: In addition to highlighting the potential for immunotherapy in BCR, this is the first study to suggest an association between the baseline microbiome and response to immunotherapy in prostate cancer. Further investigation is required to identify the interactions between specific gut microbes and activated immune response. Additional BCR immunotherapy studies (not including checkpoint inhibitors) are ongoing/planned at the NCI with serial PET imaging and microbiome sequencing. Clinical trial information: NCT03315871 .