medwireNews: The relative abundance of gut Akkermansia muciniphila (Akk) could serve as a biomarker of response to PD-1 pathway inhibition in people with advanced non-small-cell lung cancer (NSCLC), suggests a prospective cohort study.
“These results expand on previous observations that have been made in smaller cohorts of patients with NSCLC and provide evidence that gut microbiome diversity and composition, specifically the relative abundance of Akk, offer relevant information to predict survival of patients with NSCLC amenable to ICIs [immune checkpoint inhibitors],” write the researchers in Nature Medicine.
For the study, 338 patients starting first- or later-line treatment with a PD-1 or PD-L1 inhibitor (atezolizumab, nivolumab, or pembrolizumab) provided at least one baseline stool sample that underwent metagenomic shotgun sequencing followed by microbiome profiling using the MetaPhlAn pipeline.
Participants with detectable Akk at baseline had a significantly higher objective response rate (ORR) to PD-1 pathway blockade than their counterparts with undetectable Akk, at 28% and 18%, respectively.
Overall survival (OS) was likewise significantly improved in patients with versus without detectable Akk, at a median of 18.8 versus 15.4 months and a hazard ratio (HR) for death of 0.72.
The between-group differences were even more marked when considering just the 86 patients who received ICIs in the first-line setting, at ORRs for the Akk-positive and negative groups of 41% and 19%, respectively, and 12-month OS rates of 59% and 35%.
Observing an over-representation of Akk species in patients with OS less than 12 months in the detectable Akk group, Laurence Zitvogel (Gustave Roussy Cancer Campus, Villejuif, France) and co-researchers posited that “the relative abundance of Akk may influence prognosis more than its absolute presence or absence.”
And indeed, Akk-low patients – defined as those with a relative abundance at or below the multivariate cutoff of 4.799% – had significantly longer median OS, at 27.2 months, than either Akk-high patients or those with undetectable Akk, at 7.8 and 15.5 months, respectively (HRs=0.38 and 0.63).
The study also validated “the growing body of evidence linking [antibiotic] use and poor clinical outcome,” say the investigators.
Specifically, participants who had not received antibiotics in the 2 months before ICI initiation had better median OS than those exposed to antibiotics in that time frame, regardless of whether they had detectable (23.0 vs 11.2 months) or undetectable (16.0 vs 9.1 months) Akk.
Zitvogel et al therefore conclude: “It may be of utmost importance to [immunotherapy] patients, risk-stratified on the basis of shot-gun metagenomics (rather than by 16S rRNA) sequencing, to precisely quantify the relative abundance of Akk in addition to [antibiotic] use and PD-L1 expression in patients with NSCLC in prospective trials designed to discover optimal biomarkers.”
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