In patients with advanced hepatocellular carcinoma (HCC), gut microbiome characteristics differed between those who had durable responses to immunotherapy and those who did not, according to a retrospective study presented at the 2023 ASCO Breakthrough meeting.¹ The presence of Clostridium butyricum was significantly more abundant in long-term responders compared with nonresponders.

“The results of this study suggest that gut metagenomic diversities and profiles are related to response to immune checkpoint inhibitors and are potential predictive biomarkers in patients with advanced HCC. The enrichment of probiotics like Clostridium butyricum correlated with durable response, which deserves further study,” said lead author Caining Zhao, MD, of The University of Hong Kong, China.

Although immune checkpoint inhibitors are the backbone of anticancer treatment for HCC, only a percentage of patients respond over the long term. “Most efforts have been directed toward identifying biomarkers of immune checkpoint inhibitor response [lasting longer] than 6 months, [but] biomarkers that predict long-term benefits are scarce,” Dr. Zhao pointed out.

Study Details

The present study analyzed the gut commensal bacteria to assess their prospective role in outcomes of patients with HCC treated with immunotherapy. The study included 63 patients with advanced HCC who had been treated with immune checkpoint inhibitors. Fecal samples were collected from each patient for metagenomic sequencing. The linear discriminant analysis effect size was used to identify significantly diverse species in different groups.

Initially, 63 patients were classified as either responders (n = 48), which included those achieving a complete response, partial response, or stable disease for longer than 12 months, or nonresponders (n = 15), which comprised those with progressive disease within 6 months. Among responders, organisms of the Clostridiaceae family and species of the Clostridium and Citrobacter genuses were significantly enriched, whereas Phocaeicola vulgatus was abundant in nonresponders. Of the 48 responders, 41 reached 1 year of follow-up and were then reclassified as 33 long responders and 8 stable responders.

Interrogation with metagenomics found a significant difference in the composition of gut microbiota between responders and nonresponders (P = .011). Next the microbial differences among all groups were analyzed. This analysis showed a significant difference in the microbiota between long responders and nonresponders (P = .005) but no significant difference between short responders and long responders, or between short responders and nonresponders. 

DISCLOSURE: Dr. Zhao reported no conflicts of interest.

REFERENCE

1. Zhao C, Liang Z, Xu W, et al: Gut microbiome to predict durable response to immunotherapy in patients with hepatocellular carcinoma. 2023 ASCO Breakthrough. Abstract 47. Presented August 3, 2023.