Skip to main content

Abstract

Non-small-cell lung cancer (NSCLC) continues to be the leading cause of mortality related to lung cancer. Substantial advances have been made in the ability to identify oncogenic driver mutations that lead to the molecular cause in lung cancer. These new developments have led to an era of individualized medicine in NSCLC. BRAF in NSCLC is considered an oncogenic driver, which is almost always mutually exclusive from other activating mutations such as epidermal growth factor receptor (EGFR). The most common BRAF mutation, V600E (Val600Glu), is observed in 1–2% of lung adenocarcinomas. Half of BRAF mutations in NSCLC are BRAF V600E. BRAF is an oncogenic driver in the MAPK pathway (RAS-RAF-MEK-ERK-MAP). Significant adverse reactions can occur and are important to detect and manage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 59.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AEs:

Adverse events

CTCAE:

Common terminology criteria for adverse reactions

DOR:

Duration of response

IA:

Investigator assessed

IRC:

Independent review committee

NSCLC:

Non-small cell lung cancer

PFS:

Progression free survival

References

  1. Orton RCAJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W. Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J. 2005;392:249–61.

    Article  CAS  Google Scholar 

  2. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  CAS  Google Scholar 

  3. Pratilas CA, Hanrahan AJ, Halilovic E, Persaud Y, Soh J, Chitale D, Shigematsu H, Yamamoto H, Sawai A, Janakiraman M, Taylor BS, Pao W, Toyooka S, Ladanyi M, Gazdar A, Rosen N, Solit DB. Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res. 2008;68:9375–83.

    Article  CAS  Google Scholar 

  4. Becker TM, Boyd SC, Mijatov B, Gowrishankar K, Snoyman S, Pupo GM, Scolyer RA, Mann GJ, Kefford RF, Zhang XD, Rizos H. Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor. Oncogene. 2013;33:1158–66.

    Article  Google Scholar 

  5. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion-Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Swann S, Legos JJ, Jin F, Mookerjee B, Flaherty K. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444–51.

    Article  CAS  Google Scholar 

  6. Long GV, Flaherty KT, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Chiarion-Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JBAG, Hansson J, Utikal J, Ferraresi V, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, Davies MA, Lane SR, Legos JJ, Mookerjee B, Grob JJ. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol. 2017;28:1631–9.

    Article  CAS  Google Scholar 

  7. Planchard D, Besse B, Groen HJM, Souquet PJ, Quoix E, Baik CS, Barlesi F, Kim TM, Mazieres J, Novello S, Rigas JR, Upalawanna A, D’Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet. 2016;17:984–93.

    Article  CAS  Google Scholar 

  8. Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland Å, Giannone V, D’Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2017;18:1307–16.

    Article  CAS  Google Scholar 

  9. Daud A, Tsai K. Management of treatment-related adverse events with agents targeting the MAPK pathway in patients with metastatic melanoma. Oncologist. 2017;22:832–3.

    Article  Google Scholar 

  10. Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 2015;7:122–36.

    Article  CAS  Google Scholar 

  11. Common Terminology Criteria for Adverse Events (CTCAE). U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Version 4.03. 2010.

    Google Scholar 

  12. Flaherty K, Infante J, Daud A, Gonzalez R, Kefford R, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367:1694–703.

    Article  CAS  Google Scholar 

  13. Czupyrn M, Cisneros J. BRAF/MEK inhibitor therapy. Consensus statements from the faculty of the melanoma nursing initiative on managing adverse events and potential drug interactions. Clin J Oncol Nurs. 2017;21(4 Suppl):11–29. https://doi.org/10.1188/17.CJON.S4.11-29.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Helen Shih .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Shih, H. (2019). BRAF in NSCLC. In: Davies, M., Eaby-Sandy, B. (eds) Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners. Springer, Cham. https://doi.org/10.1007/978-3-030-16550-5_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-16550-5_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-16549-9

  • Online ISBN: 978-3-030-16550-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics