Performance of a multi-target, multi-cancer early detection (MCED) blood test in a prospectively collected cohort

Background: Multi-target blood tests have the potential to detect a broad range of cancer types and stages. We previously trained and independently assessed the performance of four biomarker classes for cancer detection in a retrospectively assembled case-control feasibility study. The primary aim of this study was to assess the performance of a methylation and protein (MP) classifier using samples from a large, multi-center, prospectively collected case-control study. As part of the ongoing assay development process, we also performed an exploratory analysis investigating the addition of a somatic mutation reflex approach (MP-reflex) on samples with scores below the threshold for a positive MP call but above a clear negative MP call. Patients and Methods: This study included 6,352 samples (1,438 cancer and 4,914 non-cancer) representing all stages among 21 tumor organ types divided approximately equally between a training and a test set. The sensitivity of the MP classifier was determined at a high specificity. The MP-reflex approach was investigated on MP samples at the same specificity threshold and detectable MP signals above pre-specified lower thresholds. Results: At 98.5% specificity, the observed overall sensitivity for MP biomarkers was 50.9%, with sensitivities of 15.4%, 26.1%, 38.0%, 67.8%, 85.5%, and 37.5% for stages I, I and II combined, II, III, IV, and unknown, respectively. When breast and prostate cancers were excluded from the analysis, overall test sensitivity was 56.8%, with sensitivities of 17.2%, 30.7%, 48.6%, 73.5%, 86.5%, and 40.0% for stages I, I and II combined, II, III, IV, and unknown, respectively. Conclusion: Methylation and protein biomarkers detected all cancer organ types incorporated in the analysis, including those without standard of care cancer screening options and aggressive cancers with poor 5-year survival. These results demonstrate the potential clinical validity of multi-biomarker testing for the detection of several cancer types.