Gut microbiota as a potential predictive biomarker

The diversity of gut microbiota just before treatment with a checkpoint inhibitor is of predictive value for response and progression-free survival (PFS), first results of the Japanese MONSTAR-SCREEN trial suggest. In addition, sarcopenia in cancer patients appears to be associated with the composition of the gut microbiome.

Immune checkpoint inhibitors (ICIs) have shown promising anti-tumour activity in a variety of cancer types, and gut microbiota have been shown to modulate efficacy of ICIs [1]. For example, Bifidobacterium longum, Dorea formicigenerans, and Enterococcus faecium are associated with good response of ICIs, whereas Prevotella histocola, and Bacteroidales are associated with poor response of ICIs. In addition, the diversity of the gut microbiome is regarded as predictive for favourable responses to ICIs.

MONSTAR-SCREEN is a nationwide cancer genome-screening project that prospectively assesses gut microbiota and circulating tumour (ct)DNA in 2,000 patients with advanced solid tumours, at 31 Japanese institutions. Dr Kentaro Sawada (Kushiro Rosai Hospital, Japan) reported results from an initial analysis of MONSTAR-SCREEN [2].

16S ribosomal RNA-sequencing was conducted to assess the alpha diversity index (ADI) of faecal microbiome, which was represented as an operational taxonomic unit (OTU) score (OTU-high was defined as a score >240). Microsatellite instability (MSI) and blood tumour mutational burden (TMB) status were measured at the same timepoints as the faeces collection. In addition, tissue TMB was measured using pre-treatment tissue samples. Primary endpoints of MONSTAR-SCREEN are the association between OTU status, MSI status, blood TMB, and tissue TMB status, as well as response rate (ORR) and PFS on ICIs.

A total of 167 patients were included. Most common cancer types were head and neck cancer (n=43), malignant melanoma (n=26), and gastric cancer (n=25). Of these, 136 (81%) patients received ICI alone, while 31 (19%) received ICI and chemotherapy combination. The ORR in OTU-high patients (n=52) was 35%, while that in OTU-low patients (n=115) was 17% (P=0.01). MSI status, blood TMB status, and tissue TMB status were not associated with ORR. In addition, OTU-high patients had a significantly longer PFS on ICIs than OTU-low patients (8.6 vs 2.6 months; HR 0.48; P=0.002).

“Although this was a preliminary analysis, diversity in gut microbiota just before treatment with ICIs was significantly associated with higher response and longer PFS in patients with advanced solid tumours,” concluded Dr Sawada. “These results indicate the potential of OTU as a predictive tumour-agnostic biomarker for the efficacy of ICIs.” Further study with shotgun and single cell metagenome analyses are ongoing.

In addition, Dr Zeynep Zengin (City of Hope Comprehensive Cancer Center, CA, USA) presented results of a study exploring the association between stool microbiome and sarcopenia in patients with metastatic renal cell cancer (mRCC) or metastatic breast cancer (mBC) [3]. In 82 patients (62 mRCC, 20 mBC; 37 sarcopenic, 45 non-sarcopenic) the microbiome was analysed. Species that were differentially abundant were Alistipes putredinis and Dialister sp. CAG 357 in patients with sarcopenia, and Collinsella aerofaciens in patients without sarcopenia. “More studies are needed to determine if there is a causal interplay,” concluded Dr Zengin.

1. Helmink BA, et al. Nat Med 2019;25:377–388.
2. Sawada K, et al. Gut microbiota and efficacy of immune-checkpoint inhibitors (ICIs) in patients (pts) with advanced solid tumor: SCRUM-Japan MONSTAR-SCREEN. Abstract 60MO, ESMO Congress 2021, 16–21 September.
3. Zengin Z, et al. Associations between sarcopenia and gut microbiota in patients with metastatic renal cell carcinoma and breast cancer. Abstract 1759MO, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 2021