Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial
Emiel A. De Jaeghere , Hannelore Hamerlinck , Sandra Tuyaerts , Lien Lippens , An M.T. Van Nuffel , Regina Baiden-Amissah , Peter Vuylsteke , Stéphanie Henry , Xuan Bich Trinh , Peter A. van Dam , Sandrine Aspeslagh , Alex De Caluwé , Eline Naert , Diether Lambrechts , An Hendrix , Olivier De Wever , Koen K. Van de Vijver , Frédéric Amant , Katrien Vandecasteele , Bruno Verhasselt , Hannelore G. Denys
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引用次数: 0
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).
期刊介绍:
Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published.
Research Areas Include:
• Cell and molecular biology
• Chemotherapy
• Cytology
• Endocrinology
• Epidemiology
• Genetics
• Gynecologic surgery
• Immunology
• Pathology
• Radiotherapy