Epidermal Growth Factor Receptor (EGFR) Gene Mutation Analysis, Non−Small-cell Lung Cancer (Real-time PCR, Version Two Assay)

CPT: 81235; 88381
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Test Details


  • Erlotinib Responsiveness in NSCLC, EGFR Mutation Analysis
  • Non−Small-cell Lung Cancer, EGFR Mutation Analysis
  • Osimertinib Responsiveness in NSCLC, EGFR Mutation Analysis
  • Tagrisso® Responsiveness in NSCLC, EGFR Mutation Analysis
  • Tarceva® Responsiveness in NSCLC, EGFR Mutation Analysis


The FDA approved cobas® EGFR Mutation Test v2 is a real-time PCR test for the qualitative detection of defined mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) patients. Defined EGFR mutations are detected using DNA isolated from FFPE tumor tissue or circulating-free tumor DNA (cfDNA) from plasma derived from EDTA anticoagulated peripheral whole blood. The test is indicated as a companion diagnostic to aid in selecting NSCLC patients for treatment with the targeted therapies listed in table below in accordance with the approved therapeutic product labeling:




Tarceva® (erlotinib)

Exon 19 deletions and L858

Exon 19 deletions and L858R

Tagrisso™ (osimertinib)



*The efficacy of Tagrisso™ (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be obtained.

Drug safety and efficacy have not been established for the following EGFR mutations also detected by the cobas® EGFR Mutations Test v2:




Tarceva® (erlotinib)

G719X, S768I, T790M, exon 20 insertions and L861Q

G719X, S768I, T790M, exon 20 insertions and L861Q

Tagrisso™ (osimertinib)

G719X, exon 19 deletions, S768I, exon 20 insertions, L858R and L861Q

G719X, exon 19 deletions, S768I, exon 20 insertions, L858R and L861Q


Detection of mutation is dependent on sample integrity and the amount of amplifiable DNA present in the specimen. The methods used in this assay are highly selective and, depending on the total amount of DNA present, can detect at least 5% of mutant (with the exception of the 2240_2257del18 in exon 19, which is detected at >10%) in a background of wild-type genomic DNA.


Genomic DNA was isolated from the provided tumor specimen using the Cobas® DNA Sample Preparation Kit for FFPE specimen and Cobas® cfDNA Sample Preparation Kit for plasma. Mutation detection is achieved through real-time PCR analysis on Cobas® z480 analyzer. The Cobas® EGFR Mutation Test v2 detects the following mutations: exon 18 (G719X), exon 19 (deletions and complex mutations), exon 20 (S768I, T790M, insertions) and exon 21 (L858R, L861Q).

Specimen Requirements


Formalin-fixed, paraffin-embedded (FFPE) tissue block, slides or plasma, frozen


Formalin-fixed, paraffin-embedded tissue block or four unstained slides and one matching H&E-stained slide at 5 μM, or 4 mL frozen plasma

Minimum Volume

Two unstained slides at 5 μM and one matching H&E-stained slide or 2 mL frozen plasma


Slides, blocks, or 4 mL BD® purple-top (K2 EDTA) tube. Collect three tubes of whole blood in accordance with the collection procedure specified below.


Please label each final plasma collection tube with the word "Plasma". Testing will be delayed if the tube is not labeled properly.

Blood Collection

• Blood should be collected according to your laboratory's procedure for venipuncture using only a BD purple-top (K2 EDTA) 4-mL blood collection tube. Plasma preparation should be performed within four hours after blood is collected. Store, transport, and ship plasma at frozen condition only. The plasma sample can be stored frozen at ≤-70°C for up to 12 months.

• Note: Do not freeze whole blood samples.

Plasma Specimen Preparation

• Immediately following specimen collection, label all tubes with appropriate patient identification information (two patient identifiers, minimum).

• The brake setting of the Drucker 642e at LabCorp service center is at 3 or 4 (manufacturer setting).

• Centrifuge the three, BD purple-top (K2 EDTA) blood collection tubes for 10 minutes at 1600±90 rcf. For conversion of RPM (revolutions per minute) to rcf (relative centrifugal force), refer to the centrifuge manufacturer's user manual.

• Remove blood collection tubes from the centrifuge (Plasma sample will be rejected if it is hemolyzed. Patient will be contacted).

• Using a fresh six-inch disposable transfer pipette, transfer plasma from three, 4-mL blood collection tubes to one 7.0-mL Sarstedt screw-cap, flat-bottom purple frozen transport tube (62.550.019). One 7.0-mL tube will be submitted.

• Ship and store plasma at ≤-70°C. Stable for 12 months.

Note: Take care not to disturb or transfer the buffy coat (white blood cells) layered above the red blood cells in the blood collection tube after the centrifugation.

Storage Instructions

Blocks or slides: Room temperature. Stability of FFPE block specimens stored at 15°C to 30°C for 12 months after the date of collection has been confirmed.

Five-micron sections mounted on slides may be stored at 15°C to 30°C for 60 days.

Plasma, frozen. The plasma sample could be stored frozen, at <-70°C for 12 months.

Causes for Rejection

No tumor tissue present in the provided specimen; broken or stained slides; hemolyzed blood; plasma not frozen; plasma volume <2 mL per tube; leaking or broken tubes

Clinical Information

Special Instructions

Please provide a copy of the pathology report or related ICD10 code on the requisition. EGFR test will be delayed if the pathology report and clinical indications are not received. Please direct any questions regarding this test to customer service at 800-345-4363.


Cobas® EGFR Mutation Test v2 (IVD), [package insert]. Roche, Doc. Rev 3.0, October 2016.
Jänne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small-cell lung cancer: Implications for treatment and tumor biology. J Clin Oncol. 2005;23:3227-3234. 15886310
Rosell R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (ERUTAC): a multicentre, open-label, randomized phase 3 trial. Lancet Onc. 2012;13(3):239-246. 22285168
Zhou C, Wu YL, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-802): A multicentre, open-label, randomized, phase 3 study. Lancet Onc. 2011;12:735-742. 21783417

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