Genetic testing for non-small cell lung cancer (NSCLC)

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Up to 85% of lung cancer cases are NSCLC

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Despite the fact that these histology subtypes have different origins, they are classified as NSCLC because the treatment, management, and prognosis are often similar.

Target therapy is a medicine aimed at certain molecules/proteins on the surface of cancer cells or inside, resulting in prevention of the growth and spread of cancer cells without a damage to healthy cells.

One target doesn’t fit all types of cancer. Genetic testing are used to clear up the most effective therapy. Plenty of clinical studies are being conducted constantly.

About the genetic testing for NSCLC

An NGS-based analysis that comprises genes focused on the clinical use of approved targeted medicine for NSCLC and agents from prospective clinical trials.

Changes in these genes result in tumor development and are used as diagnostic, prognostic, and predictive markers of cancer.

The assay identifies:

hotspots (SNV/indels)
copy number variations (CNV)
chromosomal aberrations (gene fusions)

Hotspots (SNV/indels)

12 genes

ALK

BRAF

CDK4

EGFR

ERBB2

FGFR2

FGFR3

KRAS

MET

PIK3CA

RET

ROS1

Copy number variations (CNV)

14 genes

ALK

BRAF

CCND1

CDK4

EGFR

ERBB2

FGFR1

FGFR2

FGFR3

FGFR4

KRAS

MET

MYC

PIK3CA

Chromosomal aberrations (Gene fusions)

13 genes

ALK

BRAF

EGFR

ERBB2

FGFR1

FGFR2

FGFR3

MET

NTRK1

NTRK2

NTRK3

RET

ROS1

Indications for genetic testing:

NSCLC patiens to::

Choose of cancer therapy
Monitor and adjust therapy in case of disease relapse

Targeted therapy for advanced or metastatic NSCLC

EGFR Exon 19 Deletion or L858R

First-line therapy

Afatinib
Erlotinib
Dacomitinib
Gefitinib
Osimertinib
Erlotinib + ramucirumab
Erlotinib + bevacizumab (nonsquamous)

Subsequent therapy

Osimertinib

EGFR S768I, L861Q, and G719X

First-line therapy

Afatinib
Erlotinib
Dacomitinib
Gefitinib
Osimertinib

Subsequent therapy

Osimertinib

EGFR Exon 20 Insertion Mutation Positive

Subsequent therapy

Amivantamab-vmjw
Mobocertinib

KRAS G12C Mutation Positive

Subsequent therapy

Sotorasib

ALK Rearrangement Positive

First-line therapy

Alectinib
Brigatinib
Ceritinib
Crizotinib
Lorlatinib

Subsequent therapy

Alectinib
Brigatinib
Ceritinibъ
Lorlatinib

ROS1 Rearrangement Positive

First-line therapy

Ceritinib
Crizotinib
Entrectinib

Subsequent therapy

Lorlatinib
Entrectinib

BRAF V600E Mutation Positive

First-line therapy

Dabrafenib/trametinib
Dabrafenib
Vemurafenib

Subsequent therapy

Dabrafenib/trametinib

NTRK1/2/3 Gene Fusion Positive

First-line/Subsequent therapy

Larotrectinib
Entrectinib

MET Exon 14 Skipping Mutation

First-line/Subsequent therapy

Capmatinib
Crizotinib
Tepotinib

RET Rearrangement Positive

First-line/Subsequent therapy

Selpercatinib
Pralsetinib
Cabozantinib

EMERGING BIOMARKERS TO IDENTIFY NOVEL THERAPIES FOR PATIENTS WITH METASTATIC NSCLC

Genetic Alteration

MET amplification
(10 copies and more)

Available Targeted Agents with Activity Against Driver Event

Crizotinib
Capmatinib
Tepotinib

Genetic Alteration

ERBB2 (HER2)

Available Targeted Agents with Activity Against Driver Event

Ado-trastuzumab emtansine
Fam-trastuzumab deruxtecan-nxki

Consulting with a clinical geneticist and/or oncologist is required to interpret test results and make a decision about cancer therapy.

This method allows to read hundreds of millions of short DNA sequences concurrently and to identify all types of mutations, including

Hotspots (SNV/indels)

Сopy number variations (CNV)

Chromosomal aberrations (gene fusions)

Technique sensitivity and specificity
Fast execution time
Concurrent identification of all types of mutations, including structural rearrangements
Minimum requirements for the quantity and quality of samples
Reducing time of analysis