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Caris Centers of Excellence Virtual Molecular Tumor Board - November 19, 2015 (No Audio)

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Slide deck from Caris Life Sciences' Virtual Molecular Tumor Board hosted by COE network member Virginia Cancer Specialists. Presented by Dr. Alex Spira

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Caris Centers of Excellence Virtual Molecular Tumor Board - November 19, 2015 (No Audio)

  1. 1. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Today’s VMTB Presented by Dr Alex Spira, M.D., PhD Director of the Research Institute and Phase I Program Virginia Cancer Specialists Agenda – Patient 1: gastric antrum tumor with FBXW7 and GNAS mutations – Patient 2: cholangiocarcinoma with RET mutation – Patient 3: EGFR-mutated NSCLC Housekeeping  Please identify yourself and organization when speaking  If you are not speaking, please make sure your phone is on mute to reduce background noise
  2. 2. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 1: gastric antrum tumor with FBXW7 and GNAS mutations
  3. 3. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • Early 70’s female presented with: – abdominal pain, nausea, 20 pound weight loss • Staging: – EGD Found to have large gastric antral mass with diffuse erythema – CT c/w gastric carcinoma and extensive liver mets • Received FOLFOX chemotherapy – PR after two cycles and continuing – Specimen sent Caris Molecular Intelligence™ profiling to explore additional treatment options
  4. 4. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 20x
  5. 5. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Caris Molecular Intelligence™ Summary • NGS – GNAS pathogenic mutation, exon 8, R201H – FBXW7 pathogenic mutation, exon 9, R465C – TP53 pathogenic mutation, exon 5, R158H – TP53 pathogenic mutation, exon 8, R273C • IHC – Sensitivities: platinum, taxanes, epirubicin – Non-sensitive: 5-FU, irinotecan, trastuzumab
  6. 6. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. FBXW7 • F-box protein • Component of ubiquitin ligase complex • Helps regulate proliferation and growth • Maintains quiescence of normal and cancer stem cells • May be associated with mTOR inhibitor response (Jardim et al, P One, 2014) (Villaruz and Socinski, Lung Cancer 2014) • Alterations implicated in multiple cancers esp. breast and GI malignancies (Takeishi et al, British J. of Cancer (2014)
  7. 7. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. GNAS Pathway
  8. 8. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Clinical Trial Options
  9. 9. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Standard therapies – Continue FOLFOX? • Clinical trials – MEK inhibitor trials? – mTOR inhibitor? • Other options?
  10. 10. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 2: cholangiocarcinoma with RET mutation
  11. 11. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • Elderly man with h/o Lung transplant on immunosuppression (prograf, prednisone) for 3 years • Diagnosis: – CT scan in follow-up showed mass in liver. – Biopsy c/w spindle cell tumor. Suspected cholangiocarcinoma. – Underwent resection c/w the same and single implant. • First CT scan 2 months later extensive metastatic disease at the surgical bed, peritoneum. • Was going to start chemo but rapid progression within two weeks and pt in hospice
  12. 12. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 20x
  13. 13. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Caris Molecular Intelligence™ Findings
  14. 14. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. RET Pathway
  15. 15. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Vandetanib • Approved in 2011 for metastatic medullary thyroid carcinoma • Activity against RET, EGFR, VEGFR • Dosage: 300 mg PO daily • Side effects: diarrhea, rash, prolonged QT interval, hypertension, and fatigue • Limited data on off-label use in GI malignancies with RET mutations
  16. 16. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 3: EGFR-mutated NSCLC
  17. 17. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • Woman, late 50’s, presented with headache and MRI c/w meningioma. – Preop chest xray shows a lung mass • Pathology revealed with NSCLC – Multiple nodes involved. • Received adjuvant chemotherapy with Cisplatin and pemetrexed x3 and Radiation to the mediastinum. – Substantial nausea • Caris Molecular Intelligence™ profiling ordered given high chance of relapse.
  18. 18. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. EGFR Pathway Results
  19. 19. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. EGFR exon 19 deletion
  20. 20. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. EGFR Resistance Mechanisms • EGFR secondary mutations – T790M ,D761Y, T854A, L747S • Amplifications – CMET, HER2, MAPK • Other mutations – KRAS, HRAS, NRAS, PIK3CA, BRAF, AXL • PTEN loss • Surviving down regulation
  21. 21. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. EGFR Resistance Mechanisms Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929287/figure/F3/
  22. 22. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Treatment options – Role for EGFR inhibitors? • Maintenance versus treat on progression – Re-test tumor if EGFR resistance develops?
  23. 23. Conclusion The next VMTB will be presented by Dr. Ed Kim of the Levine Cancer Institute the week of December 14. Look for an Outlook invitation for the next VMTB Please direct any questions regarding the VMTB to cariscentersofexcellence@carisls.com

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