What will biomarker testing uncover in your NSCLC patients?

There are more targeted therapies available today than ever before for the treatment of non–small cell lung cancer (NSCLC). In fact, up to 69% of patients with advanced NSCLC could have a potentially actionable biomarker.1

Biomarkers with approved treatments include RET, MET, EGFR, ALK, ROS1, BRAF, and NTRK.2 Researchers have identified others that still lack approved treatments, such as HER2, KRAS, and many more.2

Biomarkers
in NSCLC1,2

As our knowledge grows and we gain a deeper understanding of what drives disease, the number of known biomarkers continues to increase.1,3,4

Video: An Overview of Biomarker Testing in Metastatic NSCLC (02:41)

Why do biomarkers matter in NSCLC—and why should you test using comprehensive biomarker testing? Dr. Timothy Burns, medical oncologist at UPMC Hillman Cancer Center, gives his answers, along with how to counsel patients to wait for test results to confirm treatment, if clinically appropriate.

Talk to your pathologist or lab partners to determine how to best test for all biomarkers, including RET.

How to optimize your testing strategy

There are a few commonly used methods to assess biomarkers in eligible patients with metastatic NSCLC, such as next-generation sequencing (NGS).5*

Sample FFPE plasma
RET fusion detection May not detect RET fusions with unknown partners5
Ability to test for multiple biomarkers at the same time Yes; however, not all rearrangements are detected5
Sample FFPE
RET fusion detection May result in false positives; lack of standard test/standardized positivity cutoffs across multiple methods5
Ability to test for multiple biomarkers at the same time No; must be tested individually5
Sample FFPE plasma
RET fusion detection Can detect fusions and other alterations with a single test7‡
Ability to test for multiple biomarkers at the same time Yes; most known biomarkers identified on panel5
Multiplex PCR* FISH NGS
Sample FFPE plasma FFPE FFPE plasma
RET fusion detection May not detect RET fusions with unknown partners5 May result in false positives; lack of standard test/standardized positivity cutoffs across multiple methods5 Can detect fusions and other alterations with a single test7‡
Ability to test for multiple biomarkers at the same time Yes; however, not all rearrangements are detected5 No; must be tested individually5 Yes; most known biomarkers identified on panel5
  • FFPE=formalin-fixed paraffin-embedded; FISH=fluorescence in situ hybridization; PCR=polymerase chain reaction.
  • *Includes reverse-transcriptase PCR.
  • In the initial diagnostic setting, if following pathologic confirmation of a NSCLC diagnosis there is insufficient material for molecular analysis, cell-free/circulating tumor DNA should be used only if follow-up tissue-based analysis is planned for all patients in which an oncogenic driver is not identified.6
  • Not all types of alterations are detected by individual NGS assays and it is important to be familiar with the types of alterations identifiable in individual assays or combination(s) of assays.6

Using NGS to test for RET fusions

NGS can be DNA based and RNA based, but RNA-based platforms offer advantages in RET detection.8

Types of gene alterations detected Gene rearrangements and DNA mutations8
Fusion detection efficiency Less sensitive and can be less efficient8
Examples of NGS platforms/kits that test for RET fusions
  • Illumina TruSight Oncology assays9
  • Thermo Fisher Oncomine assays10
  • Archer Comprehensive Solid Tumor (CST)11
Types of gene alterations detected Gene rearrangements and RNA mutations8
Fusion detection efficiency More sensitive and can be more efficient8
Examples of NGS platforms/kits that test for RET fusions
  • Illumina TruSight Oncology assays9
  • Thermo Fisher Oncomine assays10
  • Archer Comprehensive Solid Tumor (CST)11
DNA-based NGS RNA-based NGS
Types of gene alterations detected Gene rearrangements and DNA mutations8 Gene rearrangements and RNA mutations8
Fusion detection efficiency Less sensitive and can be less efficient8 More sensitive and can be more efficient8
Examples of NGS platforms/kits that test for RET fusions
  • Illumina TruSight Oncology assays9
  • Thermo Fisher Oncomine assays10
  • Archer Comprehensive Solid Tumor (CST)11

If appropriate testing isn't available at your practice/institution, below are examples of NGS labs:

  • Foundation Medicine12
  • Guardant (circulating tumor DNA)13
  • Inivata (circulating tumor DNA)14
  • Resolution Bioscience (circulating tumor DNA)15
  • Caris Life Sciences16
  • Tempus17
  • NeoGenomics18
  • Integrated Oncology/LabCorp19
  • Mayo Clinic Laboratories20

Blueprint Medicines is not affiliated with these organizations and does not endorse any particular service or group.

It's now possible to assess most actionable biomarkers in NSCLC with one test.5

Performing a hot spot panel or sequential testing of specific biomarkers can diminish tissue samples and will only capture a limited number of genetic alterations.21 Exclusionary and sequential testing methods can deplete limited tissue samples, necessitate the need for additional biopsies, and slow down the process of identifying biomarkers—in turn, limiting a patient’s ability to receive the maximum benefit from first-line treatment.21

That's why the NCCN NSCLC Panel recommends molecular testing and strongly advises broader molecular profiling, such as next-generation sequencing (NGS), to identify rare driver mutations in eligible patients with metastatic NSCLC for which effective drugs may already be available.6 NGS can assess most of these actionable biomarkers with one test—so you can identify which biomarker is responsible for driving disease.5 NGS can also save time in the long run by capturing these biomarkers with one test up front.21

In special circumstances—for instance, when insufficient tissue samples are available—diagnostic techniques other than NGS may be used to identify biomarkers. These include cell-free/circulating tumor DNA (ctDNA) testing (“liquid biopsy”), multiplex polymerase chain reaction (PCR) systems, and fluorescence in situ hybridization (FISH).5

Once NGS results are in hand, you can confirm your course of therapy, knowing that it may target the driver of the patient’s disease.7

For patients who, in broad panel testing don’t have identifiable driver oncogenes (especially in never smokers), consider RNA-based NGS if not already performed, to maximize detection of fusion events.

What NCCN Guidelines® recommend

The National Comprehensive Cancer Network® (NCCN®) NSCLC Panel strongly advises that broad molecular profiling be done as part of biomarker testing using a validated test(s) that assesses a minimum of the following potential genetic variants: EGFR mutations, BRAF mutations, METex14 skipping mutations, RET rearrangements, ALK fusions, and ROS1 fusions.6

View the latest
NCCN Guidelines

Are you testing for RET?

RET is a biomarker of interest in NSCLC that warrants your attention.1,22

See why

ALK=anaplastic lymphoma kinase; BRAF=B-Raf proto-oncogene; EGFR=epidermal growth factor receptor; MET=MET proto-oncogene; NCCN=National Comprehensive Cancer Network®; NSCLC=non‐small cell lung cancer; NTRK=neurotrophic tyrosine receptor kinase; RET=rearranged during transfection; ROS1=ROS proto-oncogene 1.

References:

NCCN=National Comprehensive Cancer Network®.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.