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Caris Centers of Excellence Virtual Molecular Tumor Board - August 12, 2015
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. Case 1
Neuroendocrine tumor
The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
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. 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.
7. 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.
10. initial liver biopsy
The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
11. Follow-up biopsy
The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
12. 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.
13. 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.
14. 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.
15. Case 2
Metastatic rectal carcinoma
The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
16. 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.
17. 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.
20. Initial presentation One year later,RFA ablated metastases
5 years later- Portal HTN from
Radiation & multiple embolizations
21. 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.
22. 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.
23. Patient 3
Recurrent ovarian stromal tumor
The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
24. 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.
25. Pathology
H & E
The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
26. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
27. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
28. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
29. 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.
30. 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.