The identification of patients most likely to benefit from ICI therapy - the so-called responders - has so far relied mainly on clinical trial data. The current methods to assess the risk-benefit of ICI treatments for individual patients are based on the Programmed Death Ligand 1 (PD-L1) expression level, which can be used to aid the clinician´s decision. BiomeOne® is a non-invasive, stool microbiome-based in vitro diagnostic test. Our aim was to compare the performance of BiomeOne® and PD-L1 in a cohort of NSCLC patients.
Stool samples from 38 stage III/IV NSCLC cancer patients (22 males, 16 females, 64.06 ± 9.37 years old) were taken prior to ICI treatment initiation with an at-home sampling collection kit (Norgen Biotek). Amplicon sequencing and bioinformatic analysis was performed, followed by BiomeOne® analysis, resulting in an output probability of response. Positive PD-L1 tests were all those > 1%. Best clinical response was assessed at the end of first line therapy. Specificity and sensitivity of each test was calculated for this cohort and used to assess the accuracy of each diagnostic test.
Overall, the PD-L1 assay exhibited a sensitivity of 67.9% (95% confidence interval (CI) 50.6, 85.1) and a specificity of 50.0% (95% CI 19.0, 80.1) in predicting the response to ICI therapy. The positive predictive value (PPV) was 79.2% (95% CI 62.9, 95.4), while the negative predictive value (NPV) was 35.7% (95% CI 10.6, 60.8). The microbiome-based biomarker had an overall sensitivity of 78.6% (95% CI 63.3, 93.8) and a specificity of 50.0% (95% CI 19.0, 80.1). The PPV of BiomeOne® was 81.5% (95% CI 66.8, 96.1), while the NPV was 45.5% (95% CI 16.0, 74.9).
A microbiome-based biomarker (BiomeOne®) appears to have a higher sensitivity and PPV than the standard immunohistochemistry PD-L1 tests and may thus serve as an important companion diagnostic in the management of patients receiving immunotherapy.
The authors.
Biome Diagnostics GmbH.
B. Sladek, N. Gasche: Non-Financial Interests, Personal, Ownership Interest: Biome Diagnostics A. Valipour: Non-Financial Interests, Personal, Advisory Board: Biome Diagnostics. All other authors have declared no conflicts of interest.