Testing specifically designed to detect certain DNA mutations that lead to METex141
FoundationOne®CDx is the only FDA-approved companion diagnostic clinically validated and optimized for detecting mutations leading to MET exon 14 skipping (METex14) in metastatic non-small cell lung cancer (mNSCLC)2
The complex biological structure of METex14 requires a test that is specifically designed for its detection3,4
Skipping of exon 14 of MET is due to DNA mutations at splice sites, which flank this exon5
- DNA mutations leading to METex14 are diverse and can include a variety of substitutions or indels3,5
The FoundationOne®CDx is the only FDA-approved test that has been clinically validated to identify patients who are eligible for treatment with TABRECTA.1
It is imperative to use a test specifically designed to detect METex14 to identify patients who are eligible for treatment with TABRECTATM (capmatinib) 150 mg, 200 mg tablets3
The ability of FoundationOne®CDx to detect METex14 in patients with mNSCLC was demonstrated in a retrospective analysis1,2
FoundationOne®CDx demonstrated agreement with the RNA-based RT-PCR clinical trial assay, which confirmed METex14 for TABRECTA1,2
RT-PCR, reverse transcription-polymerase chain reaction.
The primary concordance analysis was conducted on 204 samples (78 positive and 126 negative).2
*The denominator is the total number of evaluable samples, and the numerator is the number of patients with agreement.
†Of 78 specimens available to be retested, only 73 were evaluable.
The limit of detection (LoD) of alterations assessed by FoundationOne®CDx
The LoD of alterations was assessed using a single FFPE tumor sample.2
- Five levels of MAF, with 10 replicates per level, were evaluated for a total of 50 replicates per sample2
Summary of LoD for alterations associated with METex14 CDx claims (short variants)2
<2.9% (all detected)
METex14 insertions and deletions
FFPE, formalin-fixed paraffin-embedded; MAF, mutant allele frequency; SNV, single nucleotide variant.
aLoD calculations for the CDx variants were based on the probit approach with 95% probability of detection.
bFor each sample, five levels of MAF, with 10 replicates per level, were evaluated for a total of 50 replicates per sample.
Preparing the test sample
FFPE tumor tissue specimens are collected and prepared following standard pathology practices. FFPE specimens may be received as either unstained slides or an FFPE block.6
FoundationOne®CDx uses DNA isolated from FFPE tumor tissue specimens.1
FFPE specimens, including cut slide specimens, are acceptable6
Use standard fixation methods to preserve nucleic acid integrity. Ten percent neutral-buffered formalin for 6 to 72 hours is industry standard. DO NOT use other fixatives (eg, Bouins, B5, AZF, Holland’s)6
Do not decalcify6
When feasible, please send6:
FFPE tissue block + 1 H&E slide‡
10 unstained slides (positively charged and unbaked at 4-5 microns thick) + 1 H&E slide‡
H&E, hematoxylin and eosin stained.
MINIMUM: 25 mm2
- If sending slides, provide 10 unstained slides cut at 4 to 5 microns thick to achieve a tissue volume of 1 mm3§
OPTIMUM: 30% tumor nuclei
MINIMUM: 20% tumor nuclei
Percent tumor nuclei is the number of tumor cells divided by total number of all cells with nuclei.