Immunotherapy has had limited success so far against glioblastoma, the most common and aggressive form of brain cancer.
A new study demonstrated that distinct gut microbiome signatures were present in patients with longer versus shorter survival following treatment with immune checkpoint inhibitors.
A Phase I/II clinical trial (NCT 03174197) investigating atezolizumab (anti-PD-L1) in combination with temozolomide and radiation therapy in newly diagnosed glioblastoma patients previously reported modest activity, with a median overall survival (OS) of 18 months and median progression-free survival of 10.6 months.
The trial was designed with correlative studies to better understand the mechanisms underlying resistance to immune checkpoint inhibitor therapy, including stool collection to analyse the gut microbiome, a novel approach for glioblastoma.
“Although the addition of atezolizumab to standard-of-care radiation and chemotherapy did not improve the survival of patients with newly diagnosed glioblastoma, the correlative studies have given us insights into which patients might respond better than expected to immune checkpoint inhibitor therapy,” said lead author and principal investigator Shiao-Pei Weathers, M.D., associate professor of Neuro-Oncology.
“The challenge with immune checkpoint inhibitor therapy in glioblastoma is that there are select patients who do respond, and we need to better understand what characterises these patients so we can tailor our treatment strategies.”
The study included 45 stool samples collected from patients on the study before (26 samples) and after (19 samples) treatment.
The researchers analysed the gut microbiome composition and classified the results by OS, finding distinct differences between the baseline (pre-treatment) microbiomes of patients with shorter survival versus longer survival.
The clinical trial enrolment population was representative of glioblastoma incidence: 68% men, 87% non-Hispanic white and a median age of 57.8.
Results from whole exosome and RNA sequencing on tumour tissue samples aligned with known genomic features of glioblastoma, including EGFR mutations associated with lower OS and IDH1 mutations associated with higher OS.
“We found distinct bacteria enriched in patients with long versus short survival, which is novel enough to warrant further investigation into this observation from a small sample size,” Weathers said.
“I think these findings may help increase excitement in immune checkpoint inhibitor therapy because it shows we still have a lot to learn about the gut microbiome and its potential role in response to immune checkpoint inhibitor therapy in glioblastoma.”
As a result of this study, many clinical trials for glioblastoma at MD Anderson now routinely include stool sample collection to enable correlative gut microbiome studies.
Source: MD Anderson Cancer Center
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