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Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial. | LitMetric

AI Article Synopsis

  • The PRIMMO trial explored the effects of a pembrolizumab treatment in patients with recurrent cervical and endometrial cancers, focusing on how the gut microbiome (GM) might influence treatment outcomes.
  • Researchers analyzed fecal samples from 35 patients using advanced gene sequencing techniques, finding significant differences in gut bacteria related to treatment responses and adverse events, as well as identifying two distinct bacterial clusters linked to survival rates.
  • This study provides preliminary evidence suggesting that the gut microbiome may play a role in the effectiveness and safety of pembrolizumab treatment for cervical and endometrial cancers, warranting further investigation.

Article Abstract

Background: The phase II PRIMMO trial investigated a pembrolizumab-based regimen in patients with recurrent and/or metastatic cervical (CC) or endometrial (EC) carcinoma who had at least one prior line of systemic therapy. Here, exploratory studies of the gut microbiome (GM) are presented.

Methods: The microbial composition of 77 longitudinal fecal samples obtained from 35 patients (CC, n = 15; EC, n = 20) was characterized using 16S rRNA gene sequencing. Analyses included assessment of alpha (Shannon index) and beta diversity (weighted UniFrac), unbiased hierarchical clustering, and linear discriminant analysis effect size. Correlative studies with demographics, disease characteristics, safety, efficacy, and immune monitoring data were performed.

Results: Significant enrichment in multiple bacterial taxa was associated with the occurrence or resistance to severe treatment-related adverse events (overall or gastrointestinal toxicity specifically). Consistent differences in GM taxonomic composition before pembrolizumab initiation were observed between patients with favorable efficacy (e.g., enriched with Blautia genus) and those with poor efficacy (e.g., enriched with Enterobacteriaceae family and its higher-level taxa up to the phylum level, as well as Clostridium genus and its Clostridiaceae family). Two naturally occurring GM clusters with distinct bacterial compositions were identified. These clusters showed a more than four-fold differential risk for death (hazard ratio, 4.4 [95 % confidence interval, 1.9 to 10.3], P < 0.001) and were associated with interesting (but non-significant) trends in peripheral immune monitoring data.

Conclusion: Although exploratory, this study offers initial insights into the intricate interplay between the GM and clinical outcomes in patients with CC and EC treated with a pembrolizumab-based regimen.

Trial Registration: ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).

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Source
http://dx.doi.org/10.1016/j.ygyno.2024.10.020DOI Listing

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