肠道微生物组与接受彭博利珠单抗治疗的宫颈癌和子宫内膜癌患者的预后之间的关系：来自 PRIMMO II 期试验的启示。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2024-11-07 DOI:10.1016/j.ygyno.2024.10.020

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

摘要

研究背景PRIMMOⅡ期试验研究了以pembrolizumab为基础的治疗方案，用于既往至少接受过一次系统治疗的复发性和/或转移性宫颈癌（CC）或子宫内膜癌（EC）患者。本文介绍了对肠道微生物组（GM）的探索性研究：方法：采用 16S rRNA 基因测序法对 35 名患者（CC，n = 15；EC，n = 20）的 77 份纵向粪便样本中的微生物组成进行表征。分析包括评估α（香农指数）和β多样性（加权UniFrac）、无偏分层聚类和线性判别分析效应大小。还进行了与人口统计学、疾病特征、安全性、疗效和免疫监测数据相关的研究：结果：多种细菌分类群的显著富集与严重治疗相关不良事件（总体或胃肠道毒性）的发生或耐受性有关。在开始使用彭博利珠单抗之前，疗效好的患者（如富含布劳菌属）和疗效差的患者（如富含肠杆菌科及其门级以上的高级分类群，以及梭状芽孢杆菌属及其梭状芽孢杆菌科）之间的基因组分类组成存在一致的差异。发现了两个具有不同细菌组成的天然基因改造菌群。这些菌群的死亡风险相差四倍多（危险比为 4.4 [95 % 置信区间为 1.9 至 10.3]，P尽管该研究是探索性的，但它提供了关于CC和EC患者在接受以pembrolizumab为基础的治疗方案后GM与临床结果之间错综复杂的相互作用的初步见解：试验注册：ClinicalTrials.gov（标识符 NCT03192059）和 EudraCT 注册（编号 2016-001569-97）。

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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

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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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

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