THXID^® BRAF

THXID^® BRAF is an in vitro diagnostics kit for the qualitative detection of the BRAF V600E and V600K mutations in metastatic melanoma patients. This real-time PCR test provides rapid and reliable results that help target patients with BRAF-mutant unresectable or metastatic melanoma that may be suitable for treatment with BRAF or MEK inhibitor.

• In 2013, bioMérieux launched the THXID^® BRAF kit, its first personalized medicine test, developed in collaboration with GSK, and designed to stratify malignant melanoma patients.
• This approval marks the result of a fruitful collaboration between GSK and bioMérieux. It was initiated in 2010, to develop a companion diagnostic test to detect BRAF V600E and V600K gene mutations found in several cancers, including melanoma. GSK and bioMérieux continue to collaborate on new uses of the THXID^®-BRAF assay.

About Melanoma and Metastatic Melanoma

Melanoma is the most serious and deadly form of skin cancer¹.

In 2008, the number of melanoma cases worldwide was estimated to 199,000 cases, causing 46 000 deaths².

When melanoma spreads in the body, the disease is called metastatic melanoma. Metastatic melanoma is the most severe form of skin cancer, with an average survival of only 8 months following diagnosis and overall 5-year survival of less than 10%³.

The MAP kinase pathway

BRAF kinase mutations activate a cell proliferation pathway that is critical in many cancers (MAP kinase pathway)^{4, 5}. Over 45 cancer-associated BRAF mutations have been identified⁶. The two most prominent BRAF mutations are V600E and V600K. These mutations lock the BRAF kinase in its active status, increasing its activity nearly 10-fold⁷. The V600E substitution represents nearly 90% of all identified BRAF mutations that occur in human cancer and accounts for 70 to 90% of BRAF mutant melanoma patients. The V600K mutation is found in an additional 6 to 29% of patients with a BRAF mutation⁸.

Theranostics :

With the discovery of role BRAF mutation in Metastatic Melanoma, a Theranostics approach is now possible thanks to the combination of:

• targeting patients by BRAF V600E and V600K mutation detection
• and treatment with BRAF inhibitors and MEK inhibitors

THXID^®-BRAF provides added medical value and healthcare savings by providing clinicians with more personalized information so they can target the right patient^{10, 11, 12, 13}.

THXID^® BRAF: A combination of automation and molecular biology

Easily integrated into the laboratory, THXID^® BRAF provides fast and accurate results for confident decisions.

• A complete kit from sample preparation to data analysis
• For the detection and identification of the BRAF V600E and V600K mutations
  
  • Fast : time to results within 6 hours
  • Accurate : 98 % of positive agreement vs Sanger Sequencing in BRAF V600 E and V600K mutation detection
  • Automated
• Simple, Streamlined Workflow for Accurate BRAF Mutation Analysis:
  
  • Sample Preparation
  • Real-Time PCR Amplification
  • BRAF V600 Mutation Status Report

Regulatory status: THXID^® BRAF is both CE IVD and US IVD

1. Skin Cancer Foundation. “What Is Melanoma?” Available at http://www.skincancer.org/skin-cancer-information/melanoma.
2. GLOBOCAN 2008
3. Ferlay J, Parkin DM, Steliarova-Foucher E, et al. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 2010;46:765-81
4. Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.Cell 2004;116:855-67.
5. Herbst RS, Heymach J, Lippman S. Lung cancer. N Engl J Med. 2008;359:1367-80.
6. Wellbrock C, Karasarides M, Marais R, et al. The RAF proteins take center stage Nat Rev Mol Cell Biol. 2004;5:875-885
7. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54.
8. Rubinstein J, Sznol M, Pavlick AC, et al. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med. 2010;8:67
9. Hauschild A, Grob JJ, Demidov LV, et al. Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600E-mutated melanoma. J Clin Oncol. ASCO 2012;30 (suppl; abstr. LBA8500).
10. Robert C, Flaherty KT, Hersey P, et al. METRIC phase 3 study: efficacy of trametinib, a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients with BRAFV600E/K mutant advanced or metastatic melanoma. J Clin Oncol. ASCO 2012;30 (suppl; abstr LBA8509).
11. Becerra C, Salazar R, Garcia-Carbonero R, et al. Phase II trial of figitumumab in patients with refractory, metastatic colorectal cancer (mCRC). J Clin Oncol. ASCO 2011;29 (suppl; abstr 3525).
12. Kirkwood JM, Long GV, Trefzer U, et al. BREAK-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets). J Clin Oncol. ASCO 2012;30 (suppl; abstr 8501)