Cobas EGFR mutation Test v2 was FDA-approved as qualitative liquid biopsy for actionable EGFR variants in non-small cell lung cancer (NSCLC). It generates semiquantitative index (SQI) values that correlate with mutant allele levels, but decision thresholds for clinical use in NSCLC surveillance are lacking. We conducted long-term ctDNA monitoring in 20 subjects with EGFR-mutated NSCLC; resulting in a 155 on-treatment samples. We defined optimal SQI intervals to predict/rule-out progression within 12 weeks from sampling and performed orthogonal calibration versus deep-sequencing and digital PCR. SQI showed significant diagnostic power (AUC 0.848, 95% CI 0.782-0.901). SQI below 5 (63% of samples) had 93% (95% CI 87-96%) NPV, while SQI above 10 (25% of samples) had 69% (95% CI 56-80%) PPV. Cobas EGFR showed perfect agreement with sequencing (Kappa 0.860; 95% CI 0.674-1.00) and digital PCR. SQI values strongly (r: 0.910, 95% 0.821-0.956) correlated to mutant allele concentrations with SQI of 5 and 10 corresponding to 6-9 (0.2-0.3%) and 64-105 (1.1-1.6%) mutant allele copies/mL (VAF) respectively. Our dual-threshold classifier of SQI 0/5/10 yielded informative results in 88% of blood draws with high NPV and good overall clinical utility for patient-centric surveillance of metastatic NSCLC.
Keywords: Biomarkers; Carcinoma non-small-cell lung; Circulating tumor DNA; Clinical laboratory techniques; Diagnostic techniques and procedures; Disease progression; Likelihood functions; Liquid biopsy; ROC curve; Statistics and numerical data; Tumor.
© 2024. The Author(s).