A mixed prebiotic/probiotic intervention (MBR-01) for the management of diarrhea during abemaciclib treatment of early breast cancer in postmenopausal patients: A single-center prospective case–control pilot study

Background: Adjuvant abemaciclib + endocrine therapy (ET) improves long-term outcomes in high-risk, hormone receptor–positive (HR+)/HER2-negative early breast cancer (eBC). However, treatment is frequently complicated by diarrhea, affecting adherence and quality-of-life (QoL). Increasing evidence suggests that abemaciclib-induced gastrointestinal toxicity may involve gut microbiota alterations. We conducted a prospective case-control pilot study evaluating the efficacy of MBR-01, a standardized prebiotic/probiotic formulation, in mitigating abemaciclib-induced diarrhea. Methods: We enrolled 20 postmenopausal patients with high-risk HR+/HER2-negative eBC considered unfit for adjuvant chemotherapy. Patients received abemaciclib + letrozole (control, n = 10) or abemaciclib + letrozole + MBR-01 (experimental, n = 10). The primary endpoint was the incidence and severity of diarrhea; secondary endpoints included treatment adherence, QoL assessments and exploratory baseline/week-12 microbiota characterization according to treatment arm. Trial registration number: ISRCTN11948182. Results: Diarrhea occurred in all patients. In the control group, diarrhea was predominantly grade 1 (50%) or grade 2 (40%), with one grade 3 event (10%). In the MBR-01 group, diarrhea frequency and severity were reduced by ∼70% at the end of week-12; 90% of patients experienced only grade 1 diarrhea or none by week-12, and no grade ≥3 events. Dose modification was only required in one control. Decrease in alpha-diversity and F.prausnitzii were associated with earlier diarrhea onset and longer duration; increase in E.coli correlated with higher grade events. MBR-01 supplementation seemed to preserve microbial diversity and limited E.coli expansion. QoL was significantly improved with MBR-01. Conclusion: MBR-01 may effectively mitigate abemaciclib-induced diarrhea, likely through the achievement of stabilization of gut microbiota composition. Larger prospective studies are warranted to validate these preliminary findings.