Certain Genomic Pathways of Gut Microbiome Significantly Associated With Survival in Nivolumab-Treated Patients With Gastric/GEJ Cancer

Results of the observational/translational DELIVER trial (UMIN000030850) of patients with gastric or gastroesophageal junction (GEJ) cancers who were treated with nivolumab (Opdivo) for any line of therapy indicated that multiple pathways and genus in the gut microbiome were significantly associated with survival, according to a presentation of the data at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer.

In 30 patients from the training cohort who were included in the overall survival (OS) analysis, 26 pathways and 6 genera were detected. Of these, 2 pathways of purine metabolism (HR, 0.31; 95% CI, 0.16021-0.61; P = .00064) and peptidoglycan biosynthesis (HR, 0.27; 95% CI, 0.126054-0.59; P = .00088) were confirmed to be significantly associated with treatment in the validation cohort. The genus Corynebacterium was also significant to OS in both training and validation cohorts (HR, 1.1; 95% CI, 1.04949-1.1; P = .00000869).

In the progression-free survival (PFS) analysis, 20 pathways, 9 genera, and 1 phylum were identified in the training cohort. The validation cohort confirmed the association of the nucleotide metabolism pathway (HR, 0.39; 95% CI, 0.22-0.70; P = .0013) and genus porphyromonas (HR, 3.4; 95% CI, 1.9-6.0; P = .000023) with PFS.

In this multicenter study, 501 patients were enrolled with 200 in the training cohort and 301 in the validation cohort. Of those, 190 and 277, respectively, were evaluable for clinical and genomic data.

Investigators collected stool and blood samples from participants to measure host-related factors correlating to nivolumab treatment. Data from the validation cohort were used to analyze potential biomarkers and information gathered from the validation cohort was used to confirm associations between the gut microbiome, gene polymorphisms, gene expression, and metabolites in plasma.

The eligibility criteria included having advanced gastric or GEJ adenocarcinoma, being aged 20 years or older, having a performance score of 2 or lower, and receipt of nivolumab in any line of therapy.

The primary end point was the relationship between the genomic pathway and the gut microbiome and the efficacy of nivolumab whether progressive disease or not at the first evaluation. The secondary end point was the association of clinical outcomes with the microbiome.

Patient characteristics of the training cohort included a 76% male (n = 144) population with the median age of 70 years (range, 37-90). In the validation cohort, 69% were male (n = 191) with a median age of 70 years (range, 26-90).

Although the nucleotide metabolism pathway was associated with both PFS and OS in the validation cohort, an association with OS was not observed in the validation cohort (HR, 0.30; 95% CI, 0.11-0.77; P = .012).

Nevertheless, these data taken together led the investigators to conclude that the nucleotide metabolism pathway may be an appropriate biomarker for predicting prognosis of nivolumab in this setting.

Reference

Sunakawa Y, Matoba R, Sakamoto Y, et al. Gut microbiome to predict survival time in advanced gastric cancer treated with nivolumab: the DELIVER trial (JACCRO GC-08). Ann Oncol. 2021;32(3):S223-S224. doi:10.1016/j.annonc.2021.05.017