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Caris Centers of Excellence Virtual Molecular Tumor Board - August 12, 2015

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Slide deck from Caris Life Sciences' Virtual Molecular Tumor Board hosted by COE Network member Fox Chase Cancer Center

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Caris Centers of Excellence Virtual Molecular Tumor Board - August 12, 2015

  1. 1. Virtual Molecular Tumor Board Fox Chase Cancer Center August 12, 2015 Presented by: Wafik El-Deiry, MD, PhD, FACP Professor, Hematology/Oncology Deputy Cancer Center; Director for Translational Research; Co-Program Leader, Molecular Therapeutics Patient 1: Pancreatic neuroendorcine tumor with C-KIT mutation Patient 2: Rectosigmoid junction cancer with HER2 amplication and PTEN loss Patient 3: Recurrent Sertoli-Leydig ovarian tumor with multiple cytotoxic biomarker findings and no NGS mutations The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  2. 2. Case 1 Neuroendocrine tumor The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  3. 3. Metastatic Neuroendocrine Tumor • Male in mid-forties presented with nausea and severe RUQ pain. • Received 4x cycles of Cis-Etoposide • For two years received 5FU+Streptozocine chemotherapy, PD • Obtained PR on Phase I trial of Litronesib/LY2523355 kinesin 5 inhibitor. Eventual PD with rapid growth of the liver mets • A biopsy with molecular studies was obtained • Additional alterations: MCL1 amplification, BAP1 splice site 2056+1 C>T mutation Perkins J. et al. JNCCN, 2014 The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  4. 4. Pathology H & E (previous specimen) H & E (current specimen) The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  5. 5. cKIT
  6. 6. Baseline 3 months on KIF11 inhibitor 4 months on imatinib Perkins J. et al. JNCCN, 2014 Sustained response for 2 years The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  7. 7. Imatinib-resistant clone- Bx#2 TACE => continue on Sunitinib
  8. 8. Litronesib Bx#1 Bx#2 Imatinib Sunitinib TACE The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  9. 9. initial liver biopsy The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  10. 10. Follow-up biopsy The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  11. 11. C-KIT variants Tyr823 (new variant) Activation Loop Val560 (original deletion) Bound inhibitor (active site) The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  12. 12. Secondary C-KIT mutations in exon 17 cause sunitinib resistance Heinrich et al. JCO, 2008 The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  13. 13. Molecular Tumor Summary • Recurrent neuroendocrine tumor with repeat NGS testing • Persistance of previously noted C-KIT mutation exon 11 V560del • Now with Secondary C-KIT mutation exon 17 Y823D (imatinib-resistant) The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  14. 14. Case 2 Metastatic rectal carcinoma The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  15. 15. Metastatic rectal adenocarcinoma • Male in mid-forties presented with mts rectal cancer • No Fam Hx • Laparoscopic liver resection • Rectal surgery after ~4 months of chemotherapy • For about two years, received FOLFOX-Bev chemotherapy on OPTIMOX-2 schedule. Stopped due to hypersensitivity to Oxaliplatin • Second line FOLFIRI-Bev, x 1 year • SIR embolization with Capecitabine until progression • Caris testing was ordered on the primary rectal tumor specimen The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  16. 16. Pathology H & E (10x) H & E (20x) The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  17. 17. Pathology HER2 IHC (10x) HER2 IHC (20x)
  18. 18. FOLFOX-Bev/SIR+cape Liver resection Rectal Sx FOLFIRI-Bev Trastuzumab+ MM111+paclitaxel Progressive liver Ds Caris test FOLFIRI-Bev IRI-Cet SIR embo Trastuzumab+ regorafenib Death
  19. 19. Initial presentation One year later,RFA ablated metastases 5 years later- Portal HTN from Radiation & multiple embolizations
  20. 20. Molecular Tumor Summary • NGS reveals no driver mutations (RAS WT) • HER2 amplified by FISH, over-expressed by IHC – PTEN loss by IHC suggests lack of anti-HER2 benefit • Cytotoxic biomarkers (TS and ERCC1 low) indicate potential benefit with 5-FU and oxaliplatin – Low expression of TOPO1 suggests lack of irinitocan benefit The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  21. 21. Additional references • HER2 amplification in CRC may be Rx with a combination of trastuzumab plus lapatinib: Siene, S., S. Marsoni, et al. (2015). “Trastuzumab and lapatinib in HER2-amplified metastatic colorectal cancer patients (mCRC): The HERACLES trial”. J Clin Oncol. 33 (suppl; abstr 3508). • ·Meta-analysis on TS/FU-based Rx in advanced CRC: Qiu, L., Zheng, M., et al. (2008). “Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studies”. Int J Cancer. 123:2384-2389. • ERCC1/oxaliplatin in CRC: Li, P., Y. Fang, et al. (2013). “ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy”. British J Cancer.108:1238-1244. • PTEN and lack of response to cetuximab: Negri, F.V., A. Ardizzoni, et al. (2010). “PTEN status in advanced colorectal cancer treated with cetuximab”. British Journal of Cancer. 102:162-64. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  22. 22. Patient 3 Recurrent ovarian stromal tumor The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  23. 23. Clinical Summary Demographics: Female in early twenties At diagnosis, the patient underwent exploratory laparotomy and right salpingo- oophorectomy for a 29 cm mass which was ruptured on entry. Stage IC and received 6 cycles of adjuvant chemotherapy with cisplatin and paclitaxel. Four years later the patient noted new onset abdominal pain. Imaging revealed a large supra-vesical complex mass with ascites. Ex-lap debulking with small bowel resection. Received 6 cycles of dose dense weekly paclitaxel/q 3wk carboplatin. One year later, abdominal recurrence on CT scan. Underwent ex-lap and complete debulking, cholecystectomy 3 cycles of BEP chemotherapy The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  24. 24. Pathology H & E The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  25. 25. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  26. 26. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  27. 27. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  28. 28. Molecular Tumor Summary • No relevant NGS mutations identified • EGFR IHC positive • Cytotoxic biomarkers suggest benefit for taxanes, anthracyclines, camptothecins – Predicted lack of benefit for gemcitabine The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  29. 29. The next VMTB will be presented by Sandy Swain, M.D., Medical Director of the Washington Cancer Institute at MedStar Washington Hospital Center Date: Monday September 14, 2015 Time: 5pm EST Look for an invitation coming soon! Please direct questions regarding the VMTB to cariscentersofexcellence@carisls.com 30The information contained in these slides is provided for educational purposes only and has been permanently de-identified.

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