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Lung Cancer

Lung Cancer Molecular Biomarkers

Mutation in epidermal growth factor receptor (EGFR) occurs in ~35% of non-small cell lung cancer (NSCLC) patients of East Asian origin and ~16% in Western populations 1,2. Multiple in-frame deletions in exon 19 and the p.L858R missense mutation in exon 21 comprise 90% of the mutations detected 3.

Studies have confirmed EGFR mutations as a predictive biomarker of treatment response to tyrosine kinase inhibitors (TKIs), Gefitinib and Erlotinib 4,5. As such screening for EGFR mutations in NSCLC patients is deemed necessary before offering these drugs.

Most of the patients who initially responded to Gefitinib and Erlotinib will eventually develop resistance to the drugs. Recently, a third-generation EGFR TKI, which is effective in tumours harbouring the p.T790M EGFR mutation (~50–60% of lung cancer patients 6,7,8), was approved in Australia for patients with NSCLC harbouring the EGFR T790M mutation following progression on an EGFR TKI 9.

In line with the above, a new Medicare item was recently introduced (Item 73351) to test tumour tissue that is derived from a new sample from a patient with locally advanced (Stage IIIb) or metastatic (Stage IV) NSCLC, who has progressed on or after treatment with an EGFR TKI. The test is to be requested to determine the eligibility for accessing “Osimertinib” under the Pharmaceutical Benefits Scheme (PBS) criteria.

Lung cancer therapy continues to follow the genomic testing paradigm. New guidelines recommend ROS1 and PD-L1 testing for all patients with NSCLC at baseline before treatment.

In NSCLC patients, accurate detection of both KRAS and BRAF mutations is therefore of high clinical importance for therapy selection 10,11.

References:
1. Mok TS et al., (2009) N Engl J Med 361(10):947–957.
2. Rosell R et al., (2009) N Engl J Med 361(10):958–967.
3. Pao W Miller VA. (2005) J Clin Oncol 23:2556-2568.
4. Yang CH et al., (2008) J Clin Oncol 26(16):2745–2753.
5. Sequist LV et al., (2008) J Clin Oncol 26(15):2442–2449 .
6. Thress K et al., (2015) Lung Cancer 90:509–515.
7. Wu Y et al., (2017) Br J Cancer 116:175–185.
8. Yu H et al., (2013) Clin Cancer Res 19:2240–2247.
9. AstraZeneca. (2016) TAGRISSO (osimertinib mesilate) product information.
10. Linardou H et al., (2008) Lancet Oncol 9:962–972.
11. Ohashi K et al., (2012) Proc Natl Acad Sci USA 109:E2127–2133.
12. Chao M & Gibbs P (2009) J Clin Oncol 27:e279–e280.
13. Haselmann V et al., (2018) Clinical Chemistry 64 (5):830–842.



Somatic Mutation | Solid Tissue Molecular Profiling in Lung Cancer

Lung Cancer Solid Tissue Gene Panel

Detection of EGFR mutations in exons 18, 19, 20 and 21 in NSCLC tumour tissue may assist in determining the patient’s eligibility to access treatment under the PBS when requested by an appropriate specialist.

This panel is used to detect the most clinically important actionable genomic alterations, including EGFR T790M, in the solid lung cancer tumour sample.

Gene panel includes:

EGFR PIK3CA
KRAS MEK1
NRAS AKT1
BRAF ERRB2

When to Order: At diagnosis or on therapy for treatment selection.
How to Order: Fill out our Somatic Mutation testing request form and tick the Somatic Mutation test panel required.
Turnaround Time: 5-7 business days from the sample receipt date.
Specimen Required: Formalin-fixed paraffin-embedded (FFPE) tissue of a solid lung cancer tumour.
Test Cost: Medicare rebate available if criteria is met. If criteria is not met there is an out-of-pocket fee of $400.

A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<5%).

 

"Rapid" (48-hr) EGFR T790M Mutation Analysis

This panel is used to detect EGFR mutations including T790M in a solid lung cancer tumour sample from a patient, within a 48-hour turnaround from sample receipt.

Gene panel includes:

  • EGFR Mutation Test
    - Exon 18 codon 719 (variants G719A, G719C, G719S),
    - Exon 20 codons 768 (S768I) & 790 (T790M) and insertions (5 variants),
    - Exon 21 codons 858 (L858R) & 861 (L861Q), and
    - Exon 19 deletions (36 variants).

When to Order: At diagnosis or on therapy for treatment selection.
How to Order: Fill out our Somatic Mutation testing request form and tick the Somatic Mutation test panel required.
Turnaround Time: 48 business hours from the sample receipt date.
Specimen Required: Formalin-fixed paraffin-embedded (FFPE) tissue of a solid lung cancer tumour.
Test Cost: An out-of-pocket fee of $450 applies (with partial Medicare rebate available if criteria is met).

A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<5%).

Download Somatic Mutation Brochure

Download Somatic Mutation Request Form Download Somatic Mutation Request Form (WA)

 



Aspect ctDNA Liquid Biopsy in Lung Cancer

Australian recommendations along with the NCCN Guidelines advise the use of liquid biopsy for lung cancer patients as an alternate for tissue in initial EGFR T790M testing 1,2. However, if the plasma is negative, then a tissue biopsy is recommended, if feasible.

Lung Cancer ctDNA Gene Panel

The Aspect Liquid Biopsy lung cancer ctDNA gene panel can detect actionable DNA alterations specific to lung cancer as detailed below.

Gene panel includes:

 EGFR (incl. T790M): 43 mutations across exon 19 indels, exon 20 insertions,
and substitutions across exons 18, 19, 20, and 21
 KRAS: 14 mutations across exon 2 and 3
 BRAF: 4 mutations across exon 11 and 15
 PIK3CA: 4 mutations across exon 9 and 20

When to Order: At diagnosis or on therapy for treatment selection.
How to Order: Health practitioners can order Aspect Liquid Biopsy for cancer patients using the Aspect Liquid Biopsy request form.
Turnaround Time: 5–7 business days from the sample receipt date.
Specimen Required: This test requires TWO 10ml blood samples (special tubes), which can be taken at any of our collection centres.
Test Cost: No Medicare rebate available. An out-of-pocket fee of $550 applies.

A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<2%).

References
1. John T et al., (2017) Asia-Pacific J of Clin Oncol 13:296–303.
2. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Non-small cell lung cancer (7 April 2017).
3. Premarket approval P150044 d Cobas EGFR MUTATION TEST V2. Cited 2016; Available from: https://www.accessdata.fda.gov/ scripts/cdrh/cfdocs/cfpma/pma.cfm?id¼P150044.
4. Calapre L et al., (2017) Cancer Letters 404:62–69.

"Rapid" (48-hr) ctDNA EGFR T790M Mutation Testing

Rapid Aspect Liquid Biopsy is used to detect a single gene target, EGFR p.T790M, of circulating tumour DNA (ctDNA) in a patient’s blood sample, within a 48-hour turnaround from sample receipt.

Gene panel includes:

  • EGFR mutation test
    - Exon 20 codons 790 (T790M)

When to Order: On EGFR TKI.
How to Order: Health practitioners can order Aspect Liquid Biopsy for cancer patients using the Aspect Liquid Biopsy request form.
Turnaround Time: 48 business hours from the sample receipt date.
Specimen Required: This test requires TWO 10ml blood samples (special tubes), which can be taken at any of our collection centres.
Test Cost: No Medicare rebate available. An out-of-pocket fee of $550 applies.

A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<1%).

Download Aspect Liquid Biopsy Doctor BrochureDownload Aspect Liquid Biopsy Patient Brochure

Download Aspect Liquid Biopsy Request Form


 

The content on our Molecular Cancer Services page is written by National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs, Associate Professor Mirette Saad

 

Assoc. Prof. Mirette Saad

MBBS (Hons), MD, MAACB, FRCPA, PhD
Lab: Clayton
Speciality: Chemical Pathology and Molecular Genetics
Areas Of Interest: Cancer Genetics, Antenatal Screening, NIPT, Endocrine, Fertility Testing and Research, Medical Teaching
Phone: 1300 134 111
Email: mirette.saad@clinicallabs.com.au

Associate Professor Mirette Saad is a Consultant Chemical Pathologist and the National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs. Associate Professor Saad obtained her fellowship in Chemical and Molecular Pathology with a clinical Microbiology sub-specialty in Egypt.

After several posts, she worked as a Medical Laboratory Director in private labs and as an Associate Professor and Examiner of Clinical Chemistry for postgraduate and undergraduate medical and nursing students at various institutions. Upon receiving the National Health and Medical Research (NHMRC) Scholarship in 2006, Associate Professor Saad commenced her PhD studies at Melbourne University and Peter MacCallum Cancer Institute in Cancer Genetics. Associate Professor Saad undertook her specialty training at Healthscope Pathology (now Australian Clinical Labs) and Monash Health and obtained the Chemical Pathology Fellowship (FRCPA) and the Membership (MAACB) by examination from the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) respectively.

She is currently a member of the Chemical Pathology Advisory Committee at RCPA. At Clinical Labs, A/P Saad supervises the antenatal screening program including combined First Trimester Screening and Non-Invasive Prenatal Testing (NIPT) along with the Molecular Genetic testing for hereditary disorders, personalised drug therapy and cancer.

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