NSCLC is a heterogeneous disease2
- NSCLC is divided into histological subtypes, such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma1,3
Due to the emergence of targeted therapy, NSCLC is increasingly tested and diagnosed on the molecular level1,3-17
- Although oncogenic drivers are often mutually exclusive, the presence of an oncogenic driver is not mutually exclusive with an elevated PD-L1 expression3,5,18
- Approximately half of patients with NSCLC may have an oncogenic driver and a PD-L1 expression of at least 1%19,20*
The genomic complexity of NSCLC calls for broad molecular profiling, such as next-generation sequencing (NGS), to detect the greatest range of biomarkers5
ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; ERBB2, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2; HER2, human epidermal growth factor receptor 2; KRAS, Kirsten rat sarcoma; MAP2K1, mitogen-activated protein kinase kinase 1; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping; NRAS, NRAS proto-oncogene guanosine triphosphatase; NSCLC, non-small cell lung cancer; NTRK, neurotrophic receptor tyrosine kinase; PD-L1, programmed death-ligand 1; PIK3CA, phosphatidylinositol 3-kinase catalytic alpha polypeptide; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1, tyrosine receptor kinase; TPS, tumor proportion score.
*Based on 2 separate analyses: 1) a prospective analysis conducted in ~10,000 patients analyzing PD-L1 TPS ≥1% and EGFR, ALK, or KRAS and 2) a multicenter, registrational study of 214 patients analyzing PD-L1 TPS of 1% and HER2, EGFR, ALK, KRAS, RET, MET, BRAF, or ROS1.
Features of NGS
Efficient use of tissue and the ability to use liquid biopsy if the tissue specimen is scarce21,22
Ability to detect several types of mutations, such as point mutations, insertions or deletions (indels), copy number changes, and rearrangements4,23,24
Potentially shorter time-to-test results compared with sequential testing for multiple biomarkers, according to a model developed to estimate the time-to-test results for broad molecular profiling25
A typical turnaround time of ~14 days26
NGS is reimbursed by Medicare as of March 201827
NSCLC Guidelines recommend using a broad, panel-based approach, such as NGS, to test for recommended biomarkers1,4,28
- Clinicians should obtain results from broad molecular profiling at diagnosis, if clinically feasible1
- Guidelines recommend testing for ALK, BRAF, EGFR, KRAS, METex14, NTRK1/2/3, RET, and ROS1 in eligible patients with mNSCLC1*
- Emerging biomarkers include MET amplification and ERBB2 (HER2) mutations1
Approximately 1 in 2 patients with NSCLC may have an actionable biomarker5-10,29,30†
mNSCLC, metastatic non-small cell lung cancer.
The National Comprehensive Cancer Network 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.
*The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.
†Prevalence rates are in accordance with those from The Cancer Genome Atlas (TCGA) Research Network, a joint effort between the National Cancer Institute and the National Human Genome Research Institute. To access the latest TCGA data, please visit: cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed July 7, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.
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- Oxnard GR, Lo PC, Nishino M, et al. J Thorac Oncol. 2013;8(2):179-184.
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- Gainor JF, Varghese AM, Ou SH, et al. Clin Cancer Res. 2013;19(15):4273-4281.
- Lin Q, Zhang H, Ding H, et al. J Transl Med. 2019;17(1):298.
- Tissot C, Couraud S, Tanguy R, Bringuier PP, Girard N, Souquet PJ. Lung Cancer. 2016;91:23-28.
- Karatrasoglou EA, Chatziandreou I, Sakellariou S, et al. Virchows Arch. 2020;477(2):207-217.
- Evans M, O’Sullivan B, Hughes F, et al. Pathol Oncol Res. 2020;26(1):79-89.
- Mazieres J, Peters S, Lepage B, et al. J Clin Oncol. 2013;31(16):1997-2003.
- Pennell NA. Time to end the debate on genomic testing in NSCLC. IASLC. April 15, 2020. https://www.iaslc.org/iaslc-news/ilcn/time-end-debate-genomic-testing-nsclc. Accessed June 25, 2021.
- Serrati S, De Summa S, Pilato B, et al. Onco Targets Ther. 2016;9:7355-7365.
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- Ascierto PA, Bifulco C, Palmieri G, Peters S, Sidiropoulos N. J Mol Diagn. 2019;21(5):756-767.
- Pennell NA, Mutebi A, Zhou Z-Y. JCO Precis Oncol. 2019. doi:10.1200/PO.18.00356.
- Lee Y, Clark EW, Milan MSD, et al. JCO Precis Oncol. 2020;4:1098-1108.
- AAPC Knowledge Center. Medicare now covers next generation sequencing. https://www.aapc.com/blog/44863-medicare-now-covers-next-generation-sequencing/. Accessed June 25, 2021.
- European Society for Medical Oncology Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Updated September 15, 2020. Accessed June 25, 2021. https://www.esmo.org/content/download/347819/6934778/1/ESMO-CPG-mNSCLC-15SEPT2020.pdf.
- Brustugun OT, Khattak AM, Trømborg AK, et al. Lung Cancer. 2014;84(1):36-38.
- Vaishnavi A, Capelletti M, Le AT, et al. Nat Med. 2013;19(11):1469-1472.