BLOOD-BASED GENOMIC TESTING FOR NEWLY DIAGNOSED NON SMALL CELL LUNG CANCER (NSCLC) PATIENTS

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1 BLOOD-BASED GENOMIC TESTING FOR NEWLY DIAGNOSED NON SMALL CELL LUNG CANCER (NSCLC) PATIENTS ADITHYA CHENNAMADHAVUNI, MD INTERNAL MEDICINE PGY- 3 GUNDERSEN HEALTH SYSTEM LACROSSE

2 No financial disclosures

3 Introduction Lung cancer is the 2 nd most commonly diagnosed cancer in men and women in the United States Lung cancer is the leading cause of cancer deaths in US Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers

4 Most NSCLC patients present at an advanced stage Conventional chemotherapy and most importantly targeted therapy plays an important role in advanced disease

5 Emerging Targeted Agents for Genetic Mutations Genetic Mutation EGFR ( 1 st line ) Tyrosine Kinase Inhibitors Erlotinib, Gefitinib, Afatinib ALK ( 1 st line ) Crizotinib, Ceretinib, Alectinib BRAF V 600 E / KRAS / ROS In research Progression free survival Conventional chemotherapy 5 6 months Target therapy 9 13 months Per clinical trials, source NCCN : LUX 3 TRIAL, EURTAC

6 Usual Process after Lung Cancer Diagnosis Discussion in tumor board Biopsy Initial pathology analysis ( Small VS NSCLC ) Next gen sequence analysis (Tissue genetic profiling) This takes 3 weeks

7 Current tissue testing in advanced NSCLC Up to (1/3) 33% of patients do not have sufficient tissue available to conduct molecular profiling Nearly (3/4) 75%of patients will not have mutation results available at their initial oncology consult As many as (1/4) 25% patients will begin treatment in advance of receiving their mutation results

8 Alternatives when not enough tissue obtained? What we need is a place which is most easily accessible and has this tumor DNA, RNA. That is : Your Blood

9 WHY? Dying tumor cells Release circulating tumor ct DNA, ctrna Picked up by droplet digital PCR (ddpcr) *source from Biodesix

10 Circulating Tumor DNA (ctdna) in the Blood Collected for Mutation Testing Called GeneStrat* ( By company called Biodesix ) Recently FDA approved Mainstream use of this test started earlier this year Actionable mutations: EGFR(sensitizing and resistance), ALK, KRAS, BRAF Results within 72 hours

11 GeneStrat Performance Data Comparison to Tissue Biopsy Biodesix Inc., 2970 Wilderness Place, Boulder CO EGFR Sensitizing EGFR Resistance KRAS ALK Sensitivity 95.9% 86.7% 87.9% 85% Specificity 100% 100% 100% 100% Concordance 97.6% 96.4% 94.9% 92% 151 matched pairs of tissue and blood were used for validation of EGFR and KRAS Mutations. 24 matched pairs of tissue and blood were used for validation of ALK AACR Annual Meeting, April 16th 20th, New Orleans, LA

12 Aim of the Gundersen study To see the tissue concordance in the clinical setting

13 Data collection Category Total number of patients included Number of patients 44 Not enough tissue sample 5 NSCLC 19 Mutation positive 2

14 Our Study Results Mutation EGFR + ALK Tissue Positive Tissue Negative N Test Positive Test Negative Total number of patients with NSCLC = 19 (Jan - June 2016) 4 patients were found to have T790 M mutation EGFR, and 4 with K-RAS whose significance is not known yet Insufficient data to calculate sensitivity, predictive value 100% tissue concordance

15 5/44 (12%) patients did not have enough tissue for genetic profiling during initial bronchoscopy National average is 33% (Ofiara LM, Navasakulpong A, et al Frontiers in Oncology. 2014;4:253. doi: /fonc )

16 Limitations Small sample size (Continuing to collect data) Mutations are seen in only % of NSCLC Low prevalence of the mutation may influence the predictive values of the test

17 Conclusions Reliable and efficient test when there is insufficient tissue at biopsy Results returned within 72 hours (available for initial oncology consult) Gene panel contains actionable mutations Now Medicare approved High concordance with tissue genetic results

18 THANK YOU

19 References 1. Blood-based Profiling of NSCLC with CLIA certified cell-free DNA Tests for EGFR, KRAS and BRAF Point Mutations and Utility in Clinical Practice*, Hestia Mellert, PhD, Scott Thurston, Trudi Foreman, Westen Hahn, Nicholas Dupuis, PhD and Gary A. Pestano, PhD 2. Profiling Blood from NSCLC Patients for Clinically Actionable Gene Variants using GeneStrat Hestia Mellert PhD1, Leisa Jackson1, Scott Thurston1, Kristina Koch1, Amanda Weaver 1, Jakkie Greer 1, Nicholas Dupuis PhD1, Westen Hahn1, Trudi Foreman1, Dianna Maar PhD2, Dawne Shelton PhD2, and Gary A Pestano PhD Lim, C., et.al Biomarker Testing and Time to Treatment Decision in Patients with Advanced Non-Small Cell Lung Cancer. Ann Oncol first published online April 28, Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer Adrian G. Sacher, MD; Cloud Paweletz, PhD; Suzanne E. Dahlberg, PhD; Ryan S. Alden, BSc; Allison O Connell, BSc; Nora Feeney, BSc; Stacy L. Mach, BA; Pasi A. Jänne, MD, PhD; Geoffrey R. Oxnard, MD 5. SacherAG, PaweletzC, et al. Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer. JAMA Oncol Apr 7 (epubahead of print). 6. Vogelstein B & KinzlerKW. PNAS. 1999;96(16): Oxnard GR et al. ClinCancer Res. 2014;20(6): DouillardJYet al. J ThoracOncol. 2014;9(9): MokT et al. ClinCancer Res. 2015;21(14): Maus, M, et al. Int J BiomedSci. 2012:8(1); Foreman T. et al. AACR-NCI-EORTC. Nov 7th, Boston, MA 12. Mellert H. et al. AACR-NCI-EORTC. Nov 8th, Boston, MA 13. NCCN guidelines on NSCLC. 14. LUX 3 trial 15. EURTAC trial 16. Ofiara LM, Navasakulpong A, Beaudoin S, Gonzalez AV. Optimizing Tissue Sampling for the Diagnosis, Subtyping, and Molecular Analysis of Lung Cancer. Frontiers in Oncology. 2014;4:253. doi: /fonc