Non-Small Cell Lung Cancer Molecular Markers

Determine eligibility for targeted therapy with TKI therapy

Detects EGFR mutations by pyrosequencing and ALK and ROS1 rearrangements by IHC

Determine eligibility for immune checkpoint inhibitor therapy

Companion diagnostic test to aid in prediction of response to pembrolizumab (KEYTRUDA) as first-line monotherapy for patients with NSCLC. For more information about PD-L1 testing, refer to the ARUP Consult PD-L1 Testing topic and algorithm.

Monitor therapy and evaluating emergence of therapy resistance

Patients treated with anti-EGFR TKI therapy who develop disease progression should be tested for the emergence of EGFR T790M mutation (acquired resistance mutation). Blood plasma or cerebrospinal fluid (CSF) can be tested.

For other individually orderable biomarkers, including emerging biomarkers and biomarker panels, see Related Tests.

Lung cancer is the leading cause of cancer-related mortality in the U.S. and generally responds poorly to traditional chemotherapy agents. Over 80% of lung cancer cases are classified as non-small cell lung cancer (NSCLC).  Individuals with advanced or metastatic disease should undergo biomarker testing to identify oncogenic driver mutations for which effective drugs (targeted therapy) may be available and PD-L1 expression testing to assess if immune checkpoint inhibitor therapy is an option.

Typical Testing Strategy

Minimum initial biomarkers recommended as a standard of care include EGFR and BRAF mutational status, ALK and ROS1 rearrangement status, and PD-L1 expression by IHC.  Broad molecular profiling (including NTRK genes rearrangement status) is strongly encouraged to identify other driver mutations for which effective therapy might be available. 

DISEASE OVERVIEW

Treatment Issues

Biomarker testing is a standard of care in patients with advanced or metastatic NSCLC as results determine the best first-line therapy. For more detailed information on the therapy selection process, please refer to current National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.

TEST INTERPRETATION

Results

  • Positive (eg, presence of gene mutation, gene rearrangement, gene amplification, PD-L1 expression): predicts response to targeted therapy with tyrosine kinase inhibitor (TKI) and/or immune checkpoint inhibitor therapy
  • Negative: may predict lack of benefit from targeted therapy with TKI and/or immune checkpoint inhibitor therapy

For more detailed information, please refer to the individual test background information provided with the test result.

Limitations

  • Results must be interpreted in the context of clinical findings and morphological and other relevant data.
  • Results may be compromised if the recommended tissue-fixation procedures have not been followed.
  • Each methodology has its own known limitations. For more detailed information, please refer to the individual test background information provided with the test result.
    References
Related Information
Non-Small Cell Lung Cancer - Non-Small Cell Lung Cancer Molecular Markers
PD-L1 Testing
PD-L1 Testing Algorithm