miRNA signature could supplement PD-L1 as NSCLC immunotherapy marker
medwireNews: Combining a plasma-based microRNA (miRNA) signature with tumoral tissue expression of programmed cell death ligand 1 (PD-L1) could help identify advanced non-small-cell lung cancer (NSCLC) patients who are unlikely to benefit from immune checkpoint inhibition, suggests an exploratory study.
Writing in Clinical Cancer Research, Mattia Boeri (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) and colleagues explain that although PD-L1 expression is widely used as a predictive biomarker for immunotherapy, it “exhibits limited efficacy,” and even patients with PD-L1-negative tumors have shown response to immunotherapeutic agents.
Therefore they evaluated a plasma-based miRNA signature classifier (MSC) comprising 24 immune-related miRNAs that stratify individuals into high, intermediate, and low risk categories.
Among 140 patients who received immune checkpoint inhibitors for stage III–IV NSCLC at the authors’ institution between July 2015 and May 2018, evaluable plasma and tissue samples to assess MSC risk level and PD-L1 expression, respectively, were available for 79% and 74% of patients.
The overall response rate across the whole cohort was 19%. Of note, none of the 25 responders with evaluable plasma samples were classified as high risk as per the MSC, and the likelihood of response was a significant 93% lower for patients in the high-risk than the intermediate- or low-risk categories.
The MSC risk level was also significantly associated with progression-free survival (PFS) and overall survival (OS), such that the risk for disease progression or death was reduced for the intermediate- or low-risk levels versus the high-risk level, with adjusted hazard ratios (HR) of 0.35 and 0.28, respectively.
The researchers then evaluated the effects of both the MSC risk level and PD-L1 expression among 84 patients with available data for both markers. Participants who were in the MSC high-risk category and had PD-L1 expression below 50% (ie, had no favorable markers) were a significant 88% less likely to achieve a response than patients who had one or two favorable markers (ie, either MSC intermediate or low risk and/or PD-L1 expression of at least 50%).
Furthermore, patients could be stratified into three distinct groups with regard to PFS, such that those with no, one, or two favorable markers had 1-year rates of 0%, 18%, and 39%, respectively, where the between-group differences were significant. This was also the case for OS, with corresponding 1-year rates of 0%, 44%, and 88%.
And the likelihood of disease progression was significantly lower for individuals with at least one versus no favorable marker, as was the risk for death, with corresponding HRs of 0.25 and 0.28.
The researchers conclude: “This first exploratory prospective study suggests that circulating miRNAs can supplement standard tissue biopsy in the clinical practice.
“Larger and possibly randomized studies are needed to establish the efficacy of MSC to select a subgroup of patients who do not benefit [from immune checkpoint inhibitor] treatment.”
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