Gut and oral microbiota profiling in patients (pts) with hormone receptor-positive (HR plus ) metastatic breast cancer (MBC) receiving pembrolizumab (P) plus eribulin (E): CALADRIO
Annals of Oncology(2022)
Abstract
Changes occurring in host-associated microbial communities (i.e. microbiota) may modulate responses to checkpoint blockade immunotherapy. We previously showed that anti-programmed cell death 1 protein P added to microtubule-targeting chemotherapy E has an encouraging antitumor activity in HR+ MBC pts regardless of programmed death-ligand 1 status. The CALADRIO study assessed the impact of gut and oral microbiota on clinical outcome of pts from the KELLY trial. The phase 2 KELLY trial investigated the efficacy and safety of P plus E in 44 pts with pre-treated, HR+, HER2-negative, locally recurrent inoperable or MBC (NCT03222856). Fecal and saliva samples were prospectively collected at baseline (BL), after 3 cycles, and end of treatment from a subset of pts. Tumor response was grouped into clinical benefit (CB; complete or partial responses, or stable disease [SD] ≥24 weeks) and no CB (SD <24 weeks or progressive disease) as per RECIST 1.1. Shotgun metagenomic and 16S rRNA gene sequencing were used to characterize fecal and saliva microbiota profiles, respectively. Microbiota data were analyzed using MEGAHIT, LEfSe, Wilcoxon ranked sum, and PERMANOVA methods. A total of 58 fecal and 68 saliva samples were collected. Overall P+E did not cause significant gut or oral microbiota perturbations, indicating any drug-related microbial toxicity. Across all pts, dominant gut microbiota genera included Bacteroides and Faecalibacterium, with a common oral microbe, Prevotella, also present. LeFSe analysis suggested CB was driven in part by gut-associated Bacteroides fragilis and oral-associated Streptococcus with an abundance ≥50%. Pts experiencing CB had gut and oral microbiota richness at BL and a decrease over treatment potentially related to the antibiotic usage. Several typical oral microbes in both saliva and fecal samples were also observed, suggesting a potential translocation along the oral-gut axis. These preliminary findings suggest potential avenues for downstream microbiota pts stratification before commencement of treatment. Further investigation is required in larger cohorts.
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Key words
oral microbiota profiling,metastatic breast cancer,pembrolizumab,breast cancer,eribulin,receptor-positive
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