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

What is NSCLC?

Up to 85% of lung cancers are NSCLC. Adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are the main subtypes of NSCLC.

Even though these histology subtypes have different origins, they are classified as NSCLC because the treatment, management, and prognosis are often similar.

Up to 85%

of lung cancers are NSCLC

What is Genetic testing for NSCLC?

An NGS-based assay includes a panel of genes concurred with the clinical use of approved targeted drugs and drugs from prospective clinical trials for NSCLC.

Alterations in these genes lead to tumor development and are used as diagnostic, prognostic, and predictive cancer markers.

"First Genetics Lab" performs testing using the high‑throughput sequencing system named "F‑Genetics" and reagents for high‑throughput next generation sequencing (NGS) of genes associated with human cancer genesis, that are registered as medical devices (Federal Service for Surveillance in Healthcare: РЗН 2020/10521, РЗН 2022/16970)

The assay detects:

Hotspots (SNV/InDels)
Copy number variations (CNV)
Chromosomal aberrations (Gene fusions)

Consulting with a clinical geneticist and an oncologist to interpret test results and select cancer therapy is required

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 testing

For patients diagnosed with NSCLC for:

Therapy selection
Therapy monitoring and correction if the cancer recurrence occurs
Clinical trials enrollment

Targeted therapy

Targeted therapy is the type of treatment that targets specific molecules/proteins on the cancer cell surface or inside the cancer cells, blocking the growth and spread of cancer cells and limiting damage to healthy cells.

Not all tumors have the same targets. Genetic tests are used to find out what treatment is the most effective. Many clinical studies are underway.

Targeted therapy. Indications for drugs

TARGETED THERAPY FOR ADVANCED OR METASTATIC NSCLC
(NCCN Guidelines Version 3.2022)

First-line therapy	Subsequent therapy
EGFR Exon 19 Deletion or L858R
Afatinib Erlotinib Dacomitinib Gefitinib Osimertinib Erlotinib + ramucirumab Erlotinib + bevacizumab (nonsquamous)	Osimertinib
EGFR S768I, L861Q, and G719X
Afatinib Erlotinib Dacomitinib Gefitinib Osimertinib	Osimertinib
EGFR Exon 20 Insertion Mutation Positive
	Amivantamab-vmjw Mobocertinib
KRAS G12C Mutation Positive
	Sotorasib
ALK Rearrangement Positive
Alectinib Brigatinib Ceritinib Crizotinib Lorlatinib	Alectinib Brigatinib Ceritinib Lorlatinib
ROS1 Rearrangement Positive
Ceritinib Crizotinib Entrectinib	Lorlatinib Entrectinib
BRAF V600E Mutation Positive
Dabrafenib/trametinib Dabrafenib Vemurafenib	Dabrafenib/trametinib

First-line therapy	Subsequent therapy
NTRK1/2/3 Gene Fusion Positive
Larotrectinib Entrectinib
MET Exon 14 Skipping Mutation
Capmatinib Crizotinib Tepotinib
RET Rearrangement Positive
Selpercatinib Pralsetinib Cabozantinib

EMERGING BIOMARKERS TO IDENTIFY NOVEL THERAPIES FOR PATIENTS WITH METASTATIC NSCLC

Genetic Alteration	Available Targeted Agents with Activity Against Driver Event
MET amplification ( 10 copies and more)	Crizotinib Capmatinib Tepotinib
ERBB2 (HER2)	Ado-trastuzumab emtansine Fam-trastuzumab deruxtecan-nxki

NGS method

NGS can simultaneously read hundreds of millions of short sequences of DNA and detect all types of mutations, including

Hotspots (SNV/InDels)

Copy number variations (CNV)

Chromosomal aberrations (Gene fusions)

Advantages

High sensitivity and specificity of the method
Fast turnaround time
Simultaneous detection of all types of mutations, including chromosomal aberrations
Minimum requirements for sample quantity and quality
Shorter testing times