Nearly 80% of patients currently do not have mutation results available at their initial oncology consult.1
How do we change this paradigm?
The GeneStrat® test offers accurate, non-invasive blood-based mutation results within 72 hours for patients with NSCLC. Using ddPCR to analyze cell-free DNA and RNA, the test delivers real-time information for diagnosis or therapy monitoring to identify specific driver mutations with proven clinical utility.
GeneStrat Measures Actionable Mutations that can Inform the use of Targeted Therapy
* ALK fusions (variants): EML4 (E6:A20, E13-A20, E20-A20)
† ROS1 fusions (variants): CD74 (C6:R34, C6:R32); SDC4 (S2:R32, S2:R34); SLC34A2 (S13del2046:R32, S13del2046:R34); EZR (E10:R34); TPM3 (T8:R35)
‡ RET fusions (variants): KIF5B (K15:R12, K16:R12, K22:R12, K23:R12, K24:R11, K24:R8); CCDC6 (C1:R12); TRIM33 (T14:R12)
GeneStrat Clinical Validation Data15,16
Clinical specificity for all GeneStrat mutations and fusions was 100%. Clinical sensitivity was not calculated for ROS1, RET, and BRAF due to availability of samples with rare mutations (ROS1, RET) and treatment-naive samples (BRAF).
EGFR sensitizing, EGFR T790M, and KRAS concordance studies above compared listed variants found in blood with GeneStrat to those found in tissue (n=151 evaluable matched pair samples). Analytical validation studies for these mutations showed a 0.02% LOD. EML4-ALK concordance studies above compared listed fusions found in blood with GeneStrat to known positives and negatives found using FISH and PCR based methods (n=24 evaluable matched pair samples); ALK, ROS1, and RET analytical validation studies validation studies showed a 0.2% LOD.
*The prevalence of EML4-ALK variants 1, 2, 3 represent 78.4% of the total ALK mutations16. Calculated sensitivity and concordance is based on the prevalence of the variants covered by the test.
HOW IT WORKS
Multi-omic results from Biodesix Lung Reflex testing throughout the continuum of care
Biodesix Lung Reflex™ integrates GeneStrat and VeriStrat testing from one blood draw for real-time measurement of genomic and proteomic biomarkers. For newly diagnosed patients with non-small cell lung cancer (NSCLC), GeneStrat® testing detects actionable mutations to inform targeted therapies for NSCLC. Patients with EGFR, EML4-ALK, ROS1 AND RET positive results are candidates for targeted therapies. Patients with EGFR negative results will reflex to VeriStrat® testing to better understand prognosis and find additional treatment options upon progression of disease.
Patients with a VeriStrat Good status are likely to benefit from platinum-based therapy, while a VeriStrat Poor result identifies when patients have more aggressive tumor growth, and may not respond to standard of care. These patients are candidates for broad molecular profiling to identify rare mutations that may present options for alternate therapies or clinical trials.
For monitoring progression on EGFR TKI therapy, GeneStrat provides sensitive EGFR T790M detection from blood, with no tissue re-biopsy needed. Patients with an EGFR T790M positive result are candidates for third generation EGFR-TKI therapy. Additionally, VeriStrat is predictive of therapeutic benefit from EGFR-TKIs.
To learn more about the products included as part of Biodesix Lung Reflex, click on the links below:
1. Lim, C., et.al. 2015. Biomarker Testing and Time to Treatment Decision in Patients with Advanced Non-Small Cell Lung Cancer. Ann Oncol first published online April 28, 2015
2. Gilotrif (afatinib), Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
3. Tarceva (erlotinib), OSI Pharmaceuticals Inc., Northbrook, IL, USA.
4. Iressa (gefitinib), AstraZeneca Pharmaceuticals, LP, Wilmington, DE, USA.
5. Tagrisso (osmertinib), AstraZeneca Pharmaceuticals, LP, Wilmington, DE, USA.
6. Xalkori (crizotinib), Pfizer Inc., New York, NY, USA.
7. Zykadia (ceritinib), Novartis Pharmaceuticals Corporation East Hanover, NJ, USA.
8. Alecensa (alectinib), Genentech, Inc. A Member of the Roche Group, South San Francisco, CA, USA.
9. Drilon AE, Sima CS, Somwar R, et al. Phase II study of cabozantinib for patients with advanced RET-rearranged lung cancers. J Clin Oncol 33, 2015 (suppl; abstr 8007)
10. Lee S-H, et al. Phas II study of Vandetinib in patients with non-small cell lung cancer harboring RET rearrangements. [abstract] J Clin Oncol 2016;34: Abstract 9013.
11. Hyman DM, Puzanov I, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF(V600E). N Engl J Med 2015; 373:726-736.
12. Gautschi O, et al. Target Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF cohort. J Thorac Oncol 2015;10:1451-1457.
13. Planchard D, et al. Dabrafenib in patients with BRAF (V600E)-positive advanced non-small cell lung cancer: an open-label, multcentre phase 2 trial. Lancet Oncol 2016;17:642-650.
14. Planchard D, et al. Dabrafenib plus trametinib in patients with previously treated BRAF (V600E)-mutant metastatic non-small cell lung cancer: an open-label, multcentre phase 2 trial. Lancet Oncol 2016 17:984- 993.
15. Mellert H, Foreman T, Jackson L, Maar D, Thurston S, Koch K, Weaver A, Cooper S, Dupuis N, Sathyanarayana UG, Greer J, Hahn W, Shelton D, Stonemetz P, Pestano GA: Development and Clinical Utility of a Blood-based Test Service for the Rapid Identification of Actionable Mutations in NSCLC Journal of Molecular Diagnostics 2017, [In Press].
16. Maus et.al. Identification of Novel Variant of EML4-ALK Fusion Gene in NSCLC: Potential Benefits of the RT-PCR Method. Maus MK, Stephens C, Zeger G, Grimminger PP, Huang E. Int J Biomed Sci. 2012 Mar;8(1):1-6.