Gut microbiome associated with PARP inhibitor efficacy in patients with ovarian cancer.

Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer.

Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to / mutation (/mut) status detected by ctDNA sequencing.

Results: Baseline samples were available from 23 /mut-positive patients and 33 mut-negative patients. The microbes enriched in the baseline samples with long PFS were , , , , and for mut-positive patients and for mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in mut-positive patients, whereas high abundances (≥1.11%) was significantly associated with longer PFS in mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11-0.69; p=0.014). In the last samples, the relative abundances of were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016).

Conclusion: High fecal composition of was associated with prolonged PFS in patients with mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.