Other Biomarkers in NSCLC

NCCN Guidelines® recommend broad molecular testing to identify driver mutations and help guide clinical decisions for patients with mNSCLC.1

In newly diagnosed mNSCLC, FDA-approved targeted therapy offers improved outcomes for patients whose tumors are positive for sensitizing EGFR mutations, ALK rearrangements, ROS1 rearrangements, BRAF V600E mutations, or express PD-L1.1

Over 50% of newly diagnosed patients with mNSCLC may benefit from targeted therapy2-10

 

ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; EGFR, epidermal growth factor receptor; FDA, Food and Drug Administration; PD-L1, programmed death-ligand 1; mNSCLC, metastatic non–small cell lung cancer; NCCN, National Comprehensive Cancer Network; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.

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.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V6.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed September 27, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org. 2. Sholl LM et al. J Thorac Oncol. 2015;10(5):768-777. 3. Korpanty GJ et al. Front Oncol. 2014;4:204. 4. Baumgart M et al. Expert Rev Precis Med Drug Dev. 2016;1(1):25-36. 5. Baik CS et al. Oncologist. 2017;22(7):786-796. 6. Shaw AT et al. N Engl J Med. 2014;371(21):1963-1971. 7. Bergethon K et al. J Clin Oncol. 2012;30(8):863-870. 8. Reck M et al. N Engl J Med. 2016;375(19):1823-1833. 9. Herbst RS et al. Lancet. 2016;387(10027):1540-1550. 10. Garon EB et al. N Engl J Med. 2015;372(21):2018-2028.

ALK Rearrangements

ALK is a receptor tyrosine kinase of the insulin receptor family.1 In NSCLC and other tumors, the ALK gene can undergo rearrangement, resulting in a fusion protein.1

ALK fusion proteins are oncogenic drivers, which constitutively activate multiple signaling pathways that promote tumor growth and survival.1,2

ALK rearrangements can lead to tumor cell survival and proliferation
ALK rearrangements can lead to tumor cell survival and proliferation

ALK rearrangements occur in up to 5% of patients with NSCLC.3,4

  • The most common ALK arrangement in NSCLC is the EML4-ALK fusion2

In newly diagnosed patients with mNSCLC,

Testing for ALK rearrangements can identify patients eligible for treatment with targeted treatment with ALK TKIs5

Available assays for ALK testing in NSCLC

Mutation FDA-approved diagnostics6-8
ALK rearrangement
  1. Vysis ALK Break Apart FISH Probe Kit (Abbott)
  2. VENTANA ALK (D5F3) CDx IHC Assay
  3. FoundationOne CDx

ALK, anaplastic lymphoma kinase; EML4, echinoderm microtubule-associated protein-like 4; FDA, US Food and Drug Administration; IHC, immunohistochemistry; mNSCLC, metastatic non–small cell lung cancer; TKI, tyrosine kinase inhibitor.

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.

References: 1. Shaw AT et al. Clin Cancer Res. 2011;17(8):2081–2086. 2. Shaw AT et al. J Clin Oncol. 2013;31 (8):1105-1111. 3. Korpanty GJ et al. Front Oncol. 2014;4(204):1-8. 4. Baumgart M et al. Expert Rev Precis Med Drug Dev. 2016;1(1):25-36. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non–Small Cell Lung Cancer V3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed March 1, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. 6. Vysis ALK Break Apart FISH Probe Kit [package insert]. Des Plains, IL: Abbott Laboratories; 2011.7.VENTANA ALK (D5F3) CDx Assay [package insert]. Tucson, AZ: Ventana Medical Systems, Inc.; 2017. 8.Foundation Medicine. FoundationOne CDx™ technical information. Foundation Medicine website. https://www.foundationmedicine.com/genomic-testing/foundation-one-cdx. Accessed March 16, 2018.

ROS1 Rearrangements

ROS1 is a receptor tyrosine kinase of the insulin receptor family.1 In NSCLC and other tumors, the ROS1 gene can undergo rearrangement, resulting in a fusion protein.1

ROS1 fusion proteins are oncogenic drivers, which constitutively activate multiple signaling pathways that promote tumor growth and survival.1,2

ROS1 rearrangements can lead to tumor cell survival and proliferation
ROS1 rearrangements can lead to tumor cell survival and proliferation

ROS1 rearrangements occur in 1%-2% of patients with NSCLC3

In newly diagnosed patients with mNSCLC,

Testing for ROS1 rearrangements can identify patients eligible for treatment with targeted treatment with an ALK TKI4

Available assays for ROS1 testing in NSCLC

Mutation FDA-approved diagnostics6-8
ROS1 rearrangement Oncomine™ Dx Target TestOncomine™ Dx Target Test
  • IHC, FISH, and other NGS tests are also commercially available to detect ROS1 rearrangements6,7

ALK, anaplastic lymphoma kinase; FDA, US Food and Drug Administration; FISH, fluorescent in situ hybridization; IHC, immunohistochemistry; NGS, next-generation sequencing; NSCLC, non–small cell lung cancer; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; TKI, tyrosine kinase inhibitor.

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.

References: 1. Shaw AT et al. N Engl J Med. 2014;371(21):1963-1971. 2. Chin LP et al. J Thorac Oncol. 2012;7(11):1625-1630. 3. Korpanty GJ et al. Front Oncol. 2014;4(204):1-8. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non–Small Cell Lung Cancer V3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed March 1, 2018. 5. US Food and Drug Administration. Oncomine™ Dx Target Test summary of safety and effectiveness data. FDA website. https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160045b.pdf. Published June 22, 2017. Accessed February 12, 2018. 6. Cytocell ROS1 Breakapart Probe [package insert]. Cambridge, UK: Cytocell Ltd.; 2014. 7. ROS1 (D4D6®) Rabbit mAb [Data Sheet]. Danvers, MA: Cell Signaling Technology, Inc.; 2016.

BRAF V600E Mutation

BRAF is a serine/threonine kinase that is part of the MAPK signaling pathway.1 In NSCLC and other tumors, mutations in BRAF are common.1

 

 

BRAF mutations lead to constitutive activation and sustained signaling of the MAPK pathway, which promotes tumor cell growth and survival.1-3

BRAF V600E mutations can lead to tumor cell survival and proliferation in non-small cell lung cancer (NSCLC)
BRAF V600E mutations can lead to tumor cell survival and proliferation in non-small cell lung cancer (NSCLC)

 

BRAF V600E mutations occur in up to 2% of patients with mNSCLC.2

  • BRAF mutations (V600E and non-V600E) occur in up to 5% of patients with mNSCLC1,3

 

In newly diagnosed patients with mNSCLC, Testing for the BRAF V600E mutation can identify patients eligible for treatment with combination BRAF and MEK inhibitor therapy.4

Available assays for BRAF testing in NSCLC

Mutation FDA-approved diagnostics5,6
BRAF V600E
  • Oncomine™ Dx Target Test
  • FoundationOne CDx™

BRAF, v-Raf murine sarcoma viral oncogene homolog B; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; mNSCLC, metastatic non–small cell lung cancer.

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.

References: 1. Nguyen-Ngoc T et al. J Thorac Oncol. 2015;10(10):1396-1403. 2. Baik CS et al. Oncologist. 2017;22(7):786-796. 3. Oxnard GR et al. J Clin Oncol. 2013;31(8):1097-1104. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V6.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed September 27, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org. 5. US Food and Drug Administration. https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160045b.pdf. Published June 22, 2017. Accessed February 12, 2018. 6. Foundation Medicine. https://www.foundationmedicine.com/genomic-testing/foundation-one-cdx. Accessed March 16, 2018.

MET, RET, HER2, and KRAS: Emerging Biomarkers

CAP/IASLC/AMP guidelines recommend testing patients with mNSCLC for MET, RET, HER2, and KRAS mutations as part of larger testing panel or when EGFR, ROS1 and ALK are negative.1

For these patients, emerging biomarkers provide predictive and prognostic value and targeted treatment under clinical investigation offer promise in the future.2

ALK, anaplastic lymphoma kinase; AMP, Association for Molecular Pathology; CAP, College of American Pathologists; EGFR, epidermal growth factor receptor; IASLC, International Association for the Study of Lung Cancer; HER2, human epidermal growth factor receptor 2; KRAS, Kirsten rat sarcoma viral oncogene homolog; MAPK, mitogen-activated protein kinase; MET, tyrosine-protein kinase Met; mNSCLC,metastatic non–small cell lung cancer; PI3K, phosphoinositide 3-kinase; RET, Ret proto-oncogene; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; TKI, tyrosine kinase inhibitor.

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.

References: 1. Lindeman NI et al. Arch Pathol Lab Med. 2018. doi:10.5858/arpa.2017-0388-CP. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non–Small Cell Lung Cancer V3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed March 1, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. Baumgart M et al. Expert Rev Precis Med Drug Dev. 2016;1(1):25-36. 4. Soo RA et al. J Thorac Oncol. 2017;12(8):1183-1209. 5. Salgia R. Mol Cancer Ther. 2017;16(4):555-565. 6. Tomasini P et al. Oncologist. 2016;21(12):1450-1460. 7. Sholl LM et al. J Thorac Oncol. 2015;10(5):768–777.