OFFERS ACTIONABLE, BLOOD-BASED MUTATION RESULTS
FOR PATIENTS WITH NSCLC FROM A SIMPLE BLOOD DRAW
OFFERS ACTIONABLE, BLOOD-BASED
MUTATION RESULTS FOR PATIENTS
WITH NSCLC FROM A SIMPLE
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 Liquid Biopsy Measures Actionable Mutations that can Inform the use of Targeted Therapy
GeneStrat delivers comprehensive results, including: EGFR, ALK, ROS1, RET, KRAS and BRAF
* 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
Validation data on the mutations included in GeneStrat show high clinical sensitivity, specificity and concordance for actionable mutations and fusions for patients with non-small cell lung cancer.
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
Biodesix Lung Reflex® Blood-based Results in 72 Hours Expedite Time to Treatment for NSCLC Patients17
Biodesix Lung Reflex® integrates GeneStrat® and VeriStrat® testing from one blood draw for real-time measurement of genomic and proteomic biomarkers. Biodesix Lung Reflex provides fast, blood-based results and saves tissue for other testing, such as the tissue-based PD-L1 expression test*.
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 positive results are candidates for targeted therapies. Patients with EML4-ALK, ROS1, RET or BRAF mutations are also targeted therapy candidates. Patients with EGFR negative results will reflex to VeriStrat testing to identify aggressive tumor growth and facilitate patient-physician conversations about treatment, prognosis, and care preferences.
Clinical data supports that patients with a VeriStrat Good result are likely to derive benefit from platinum-based therapy, while those with a VeriStrat Poor result are less likely to respond to platinum-based therapy. PD-L1 tissue results, available from multiple vendors, may be considered for these patients, depending on patient history and other factors. For patients who express PD-L1 at ≥50%, single-agent immunotherapy may be a lower toxicity option. For those who express PD-L1 at <50%, more aggressive treatment through novel therapies and combinations, such as a platinum doublet with immunotherapy (immunotherapy triplet), may be a treatment choice. Additionally, broad molecular profiling to identify rare mutations 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.
For monitoring progression of patients with EGFR negative results, VeriStrat provides important prognostic information and is also predictive of therapeutic benefit from EGFR-TKIs.
*PD-L1 tissue testing is not available through Biodesix. Testing can be conducted through multiple vendors; turnaround time for results may vary.
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. Phase II study of Vandetanib 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, multicentre 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, multicentre phase 2 trial. Lancet Oncol 2016 17:984- 993.
15. Mellert, H., Foreman, T., Jackson, L. et al. (2017, May). Development and Clinical Utility of a Blood-Based Test Service for the Rapid Identification of Actionable Mutations in Non-Small Cell Lung Carcinoma. Journal of Molecular Diagnostics, 19(3), 404-416.
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.
17. Bowling M, et al. (2016, September). Poster presentation: IASLC, CMSTO, Chicago, IL. Abstract 143. Poster PS01.16.