Table 3.

Comparison of tissue versus cfDNA results for the guideline-recommended biomarkers in newly diagnosed metastatic NSCLC with FDA-approved therapies, EGFR exon 19 deletion and L858R, ALK fusion, ROS1 fusion, and BRAF V600E

Tissue+Tissue−Tissue not assessedTissue QNSTotal
EGFR exon 19 delcfDNA+1800119Sensitivity81.8%
cfDNA−42011925249PPV100.0%
cfDNA TND0111113Specificity100.0%
cfDNA cancelled00101NPV98.0%
Total222122127282Concordance98.2%
EGFR L858RcfDNA+900211Sensitivity90.0%
cfDNA−12131924257PPV100.0%
cfDNA TND0111113Specificity100.0%
cfDNA cancelled00101NPV99.5%
Total102242127282Concordance99.6%
ALK fusion (original)cfDNA+50016Sensitivity62.5%
cfDNA−32072725262PPV100.0%
cfDNA TND1102013Specificity100.0%
cfDNA cancelled01000NPV98.6%
Total92182926282Concordance98.6%
ALK fusion (reanalysis)cfDNA+60017Sensitivity75.0%
cfDNA−22072725261PPV100.0%
cfDNA TND1102013Specificity100.0%
cfDNA cancelled01001NPV99.0%
Total92182926282Concordance99.1%
ROS1 fusioncfDNA+00000Sensitivity-
cfDNA−21518530268PPV-
cfDNA TND075113Specificity100.0%
cfDNA cancelled01001NPV98.7%
Total21599031282Concordance98.7%
BRAF V600E mutationcfDNA+20002Sensitivity100.0%
cfDNA−09015818266PPV100.0%
cfDNA TND058013Specificity100.0%
cfDNA cancelled00101NPV100.0%
Total29516718282Concordance100.0%
  • NOTE: Overall concordance across all four genes was greater than 98.2%, with a PPV of 100%. With continuous assay improvements, one cfDNA result originally reported as a false-negative for ALK fusion was identified as positive.