In the US, lung cancer accounts for approximately 13% of all cancer diagnoses but about 22% of all cancer deaths, which is more than all breast, colorectal, and prostate cancer deaths combined.1 Lung cancer comprises different tumor types, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which are the most common.2 NSCLC accounts for approximately 85% of all lung cancers.3 There is a general consensus among clinical practice guidelines and national medical societies that biomarkers including epidermal growth factor receptor (EGFR) should be assessed to identify patients who are likely to benefit from biomarker targeted treatment.4

The 5-year survival rate for patients with NSCLC is approximately 24% for all stages.1 Although survival is lowest in Stage IV disease, mortality is still considerable for patients diagnosed with earlier stages of disease.5,6

Types of Lung Cancer

Types of Lung Cancer
Types of Lung Cancer

NSCLC by Stage of Disease

NSCLC by Stage of Disease
NSCLC by Stage of Disease

aBased on the clinical staging of the 7th edition International Association for the Study of Lung Cancer (IASLC). The database includes patients diagnosed between 1999 and 2010 and treated using all modalities of care.6 bEstimated from Surveillance, Epidemiology, and End Results Program validation set of proposed 8th edition IASLC staging.5 cOverall survival by clinical stage. dIncludes Stages IA1, IA2, and IA3 according to the 8th edition IASLC staging classification.6 eIncludes Stages IIIB and IIIC according to the 8th edition IASLC staging classification.6

Genetic alterations and abnormal gene expression contribute to pathogenesis of NSCLC.8 Recognition that a molecular alteration can drive tumorigenesis and predict response to a targeted therapy has opened the door for biomarker-driven treatment in metastatic NSCLC (mNSCLC).9 The US Food and Drug Administration (FDA) has approved a number of targeted therapy drugs or drug combinations for metastatic NSCLC, highlighting the importance of accurate biomarker testing.10 These therapeutic options may be evaluated by FDA-approved companion diagnostic tests.11

Approximately 1 in 3 patients with adenocarcinoma has a potentially actionable mutation8,12,13,a

Approximately 1 in 3 patients with adenocarcinoma has a potentially actionable biomarker
Approximately 1 in 3 patients with adenocarcinoma has a potentially actionable biomarker
ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; KRAS, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; MET, mesenchymal-epithelial transition; NTRK, neurotrophic tyrosine receptor kinase; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.
aBased on 3 studies of patients with lung adenocarcinoma.8,12,13 Sholl et al, 2015 included 733 patients with lung adenocarcinoma but did not test patients for ROS1 rearrangements or NTRK fusions.8 Stransky et al, 2014 analyzed 513 samples from patients with lung adenocarcinoma.12 Bergethon et al, 2012 screened 694 patients with lung adenocarcinoma for ROS1 rearrangement status.13 bPercentage adjusted based on aggregate of Sholl et al, Stransky et al, and Bergethon et al.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommendations for Testing

NCCN Guidelines® recommend testing eligible patients with resectable Stage IB-IIIA NSCLC for EGFR mutations and also recommend broad panel-based biomarker testing, typically performed by next-generation sequencing (NGS), at diagnosis of certain patients with metastatic NSCLC to help determine appropriate treatment options.14,15 Diagnostic and biomarker testing require a multidisciplinary approach, with appropriate sample acquisition and handling.16,17 In resectable Stages IB-IIIA NSCLC, surgical tissue or biopsy specimens may be used for testing.14 For eligible patients with metastatic NSCLC, histologic, cytologic, and liquid biopsy (plasma testing) specimens may be used for molecular testing, and when clinically feasible, know all biomarker test results for actionable biomarkers before initiating first-line treatment.14,18

NCCN Guidelines Recommend Biomarker Testing for Resectable Stage IB-IIIA and Metastatic NSCLC to Help Determine Appropriate Treatment Options14

NSCLC Guidelines for Testing
NSCLC Guidelines for Testing

Refer to the NCCN Guidelines® for specific treatment recommendations for each setting. Not all agents in a drug class are recommended for all settings.

ADC, adenocarcinoma; PD-L1, programmed death-ligand 1; SCC, squamous cell carcinoma.
aTesting is recommended for EGFR mutations on surgical tissue or biopsy in Stages IB-IIIA. bThe NCCN Guidelines for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays. cA specific adjuvant EGFR tyrosine kinase inhibitor is recommended for certain patients with completely resected Stage IIB-IIIA or high-risk Stage IB-IIA NSCLC. dThe NCCN NSCLC Guidelines Panel recommends biomarker testing in eligible patients with metastatic NSCLC and strongly advises broader molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available, or to appropriately counsel patients regarding the availability of clinical trials. Broad molecular profiling is a key component of the improvement of care of patients with NSCLC. eIf there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, MET, NTRK1/2/3 and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2021. ©2021 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.

EGFR Mutation
EGFR Mutation

Learn More About EGFR Mutations and Other Biomarker Testing for NSCLC

Molecular characterization of resectable Stage IB-IIIA NSCLC through EGFR biomarker testing and metastatic NSCLC through biomarker testing guides optimal treatment decisions and clinical trial enrollment.10,19 Approximately 60% of molecular alterations in lung adenocarcinoma can guide treatment in metastatic NSCLC, with activating mutations in EGFR being one of the most common actionable mutations among patients with NSCLC adenocarcinomas.8,12,13,a

aBased on 3 studies of patients with adenocarcinoma.8,12,13 Sholl et al, 2015 included 733 patients with lung adenocarcinoma but did not test patients for ROS1 rearrangements or NTRK fusions.8 Stransky et al, 2014 analyzed 513 samples from patients with lung adenocarcinoma.12 Bergethon et al, 2012 screened 694 patients with lung adenocarcinoma for ROS1 rearrangement status.13

Multidisciplinary Collaboration for Testing

The era of targeted therapy has introduced the need for comprehensive biomarker testing in routine clinical practice.18

The complex biomarker testing process requires coordinated collaboration across specialties for patients with NSCLC16,18,20,21

NSCLC Multidisciplinary Collaboration for Testing
NSCLC Multidisciplinary Collaboration for Testing

MDT, multidisciplinary team; NSCLC, non-small cell lung cancer.

1. American Cancer Society. Cancer Facts & Figures 2020. American Cancer Society; 2020. Accessed October 20, 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. 2. American Cancer Society. What is lung cancer? Accessed October 20, 2020. https://www.cancer.org/cancer/lung-cancer/about/what-is.html. 3. EpiCast Report: Non-Small Cell Lung Cancer (NSCLC) – Epidemiology Forecast to 2025. New York, NY: GlobalData; November 2016. 4. Leighl NB, et al. Clin Cancer Res. 2019;25(15):4691-4700. 5. Deslypere G, et al. Ther Adv Med Oncol. 2018;10:1-11. 6. Goldstraw P, et al. J Thorac Oncol. 2016;11(1):39-51. 7. Heist RS, Engelman JA. Cancer Cell. 2012;21(3):448.e2. 8. Sholl LM, et al. J Thorac Oncol. 2015;10(5):768-777. 9. Baumgart M, Pandya K. Exp Rev Precis Med Drug Dev. 2016;1(1):25-36. 10. Arbour KC, Riely GJ. JAMA. 2019;322(8):764-774. 11. US Food and Drug Administration. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). Accessed October 26, 2020. https://www.fda.gov/medical-devices/vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-vitro-and-imaging-tools. 12. Stransky N, et al. Nat Commun. 2014;5:4846. 13. Bergethon K, et al. J Clin Oncol. 2012;30(8):863-870. 14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2021. ©National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 4, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 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. 15. Lindeman NI, et al. Arch Pathol Lab Med. 2013;137(6):828-860. 16. Levy BP, et al. Oncologist. 2015;20(10):1175-1181. 17. Ofiara LM, et al. Front Oncol. 2014;4:253. 18. Lindeman NI, et al. Arch Pathol Lab Med. 2018;142(3):321-346. 19. Pennell NA, et al. Am Soc Clin Oncol Educ Book. 2019;39:531-542. 20. Cree IA, et al. J Clin Pathol. 2014;67(11):923-931. 21. Pirker R, et al. J Thorac Oncol. 2010;5(10):1706-1713. 22. Gregg JP, et al. Transl Lung Cancer Res. 2019;8(3):286-301. 23. Aisner D, Marshall CB. Am J Clin Pathol. 2012;138(3):332-346. 24. Jenkins J. Semin Oncol Nurs. 2011;27(1):64-71.