School of Medicine, Texas A&M Health Science Center, Bryan, TX, 77807, USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St, 2nd Fl, San Francisco, CA, 94158, USA.
J Cancer Res Clin Oncol. 2023 Aug;149(10):7355-7362. doi: 10.1007/s00432-023-04656-8. Epub 2023 Mar 16.
Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment.
Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies.
The search for interventional trials produced 205 articles, 3 of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3 months, and a median overall survival (OS) of 7 months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7 months vs. 2.5 months in patients receiving nivolumab-ipilimumab plus CBM588 compared with patients receiving nivolumab-ipilimumab alone respectively, and an undefined median OS.
Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.
胃肠道（GI）微生物组调节剂，如粪便微生物组移植（FMT），被认为是标准免疫检查点抑制剂（ICI）治疗的补充，以提高疗效。本系统评价旨在评估使用 FMT 增强 ICI 治疗的临床试验的研究设计和结果。
使用包括 ICI 和胃肠道微生物组名称的搜索词，在 PubMed 和 Embase 上进行系统文献检索。第一次搜索确定了干预性试验，第二次搜索确定了干预性、回顾性和观察性研究。
干预性试验的搜索产生了 205 篇文章，其中 3 篇符合纳入标准。所有研究的样本量均在 10 至 30 名参与者之间。2 项研究为无对照臂的单臂研究。一项研究报告了 15 例中的 3 例（20%）总缓解率（ORR）、3 个月的中位无进展生存期（PFS）和 7 个月的中位总生存期（OS）。第二项研究报告了 10 例中有 1 例（10%）完全缓解和 10 例中有 2 例（20%）部分缓解。第三项研究报告了接受 nivolumab-ipilimumab 加 CBM588 治疗的患者的 ORR 为 58%，而接受 nivolumab-ipilimumab 单药治疗的患者为 20%，中位 PFS 分别为 12.7 个月和 2.5 个月，接受 nivolumab-ipilimumab 加 CBM588 治疗的患者的中位 OS 未定义。
目前关于免疫检查点抑制剂联合使用微生物组调节剂的研究在研究设计上受到限制。未来的临床试验应采用随机方法、使用更大的样本量，并使用适当的对照臂，以更好地确定胃肠道微生物组对 ICI 治疗的临床效果。
