Caris Centers of Excellence Virtual Molecular Tumor Board Fox Chase - Jan 26, 2016 (No Audio)

The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
Virtual Molecular Tumor Board
Fox Chase Cancer Center
January 26, 2016
Presented by: Namrata Vijayvergia, M.D.
Patient 1: Gastro-esophageal adenocarcinoma with EGFR amplification
Patient 2: Peritoneal carcinomatosis from upper GI primary with BRAF mutation
Patient 3: Pancreatic adenocarcinoma with BRCA2 mutation

Patient 1

The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
History
• Male, late 60’s, presented with abdominal pain, weight gain
• Diagnostic Workup:
– CT: celiac nodes, liver masses and retroperitoneal nodes, and mass
suggesting Gastroesophageal junction adenocarcinoma
– Liver biopsy: upper GI adenocarcinoma with moderate differentiation
– EGD with biopsy confirmed GE junction cancer
• Initial specimen HER2 2.0 by FISH and 2+ IHC
• Dx: Stage 4 GE junction cancer, metastatic to liver and nodes

Pathology
H & E 20x

FOLFOX+T
(11 months)
Docetaxel
(2 months)
FOLFIRI
(3 months)
Case #1. Male, late 60’s, with metastatic esophageal adenocarcinoma.
HER2 testing: IHC 2+ (equivocal); Ratio 2.0 by ISH (positive) @ Integrated Oncology
Second biopsy: HER2 IHC 1+ (20%); Ratio 1.36 (negative)
EGFR IHC 2+ (60%); Ratio 12.67 (amplified)
+ 2 months

Repeat Biopsy

Nature, 2014
TCGA data on gastric cancer

Mutation Count vs CNA
0.0 0.2 0.4 0.6 0.8
1
10
100
1000
10000
#ofmutations
Four molecular subclasses of GC
Genome unstable (MSI)
Chromosome instability (CIN)
Genome stable (diffuse)
Epstein-Barr virus+

EG AC mutations (TCGA, 2014)
RTK
MAPK
DDR
Epi

Epidermal growth factor receptor copy number gain (EGFR CNG) and
response to gefitinib in oesophageal cancer (OC): Results of a
biomarker analysis of a phase III trial of gefitinib versus placebo
(TRANS-COG)
Dutton S.J. Lancet Oncol. 2014 Jul;15(8):894-904
• Gefitinib single agent therapy in 450 pts with Mts EC.
• EGFR FISH results for 295 patients
• EGFR amplifications in 48/295 (16.3%)
• In EGFR-amp. OS improved (HR=0.52, CI=0.28-0.96, p=0.033)
• Survival for G. vs. P. 9 months- 27 vs.5%, 12 months-13 vs.0%
• No difference in EGFR normal CN.
• EGFR amplification (6%) pts gained greatest benefit from G.
(OS, HR=0.19, 95% CI=0.05-0.65, p=0.007).
Abstract, R. Petty et al.

Discussion
• Erlotinib in setting of EGFR amplification
• Clinical outcomes with EGFR amplification vs. mutation
– Erlotinib is recognized on Lung NCCN compendium for EGFR
amplification
– Report of about of at least 29% GE junction tumors with EGFR
expression (Sgroi, ASCO 2008)
• Future treatment options
– TOP2A / anthracyclines?
– MGMT / temozolomide?
– Available studies

Patient 2

History
• Female, late 70’s
• PMH: stage one rectal carcinoma, COPD, psoriarsis,
GERD, bronchiectasis
• FH: MGM with colon cancer, sister with Gyn cancer
• ECOG 1 performance status
• Now with peritoneal carcinomatosis and liver
metastasis of upper GI/pancreaticobiliary origin
• Initial CEA: 13.5, CA-19-9: 141

Treatment History
• Started on FOLFOX
– Required dose reduction of oxaliplatin (cytopenia)
– Also some infusion reaction
• After 5 months
– Some clinical improvement
– Markers reduced:
• CEA: 4.0
• CA-19-9: 62

Pathology
H & E 20x TS 20x

Molecular Tumor Summary

BRAF Inhibitors
Dabrafenib

Discussion
• Role of BRAF inhibitors in upper GI cancers?
– Mutations reported in about 13% of pancreatic cancers
especially with acinar differentiation (Jiao et al, J Pathol, 2014)
– Rare in biliary (<1%) (Goeppert et al, Mod Pathol, 2014)
– Unknown outcomes with BRAF inhibitors
• Low Thymidylate Synthase (TS):
– Suggests ongoing role for 5-FU-based therapy
– Clinically responding to FOLFOX
– TOPO1 predicts lower chance of irinotecan response

Patient 3

History
• Female, late 40’s, with abdominal pain and bloating
• PMH: Hodgkins stage 2A during twenties
• FH: unremarkable
• Workup:
– CT revealed pancreatic mass and liver lesions
– EUS/biopsies revealed carcinoma of duodenal wall and pancreas, gastric
wall negative for malignancy
• Dx: Pancreatic/duodenal adenocarcinoma
– Poorly differentiated, With Squamous feature
– Stage 4

Pathology
H & E 40x PD-L1 40x

Molecular Tumor Summary
NGS
• BRCA2 S1982fs exon 11 pathogenic mutation
• PIK3CA G1007R exon 21 pathogenic mutation
• KRAS G12V exon 2 pathogenic mutation
PD-L1 positive by IHC

Discussion
• Management of BRCA2 mutation
– Genetic counseling implications
– Germline confirmation?
– Role for PARPi?
– 21% response rate to olaparib monotherapy in pancreatic
patients with BRCA2 germline mutations (Kaufman JCO 2015)
– Mitomycin-C (9-12 week response) (Vyas, Anti-Cancer Drugs 2015)
• PDL1 positive: Role for immunotherapy?
• KRAS exon 2 mutation
• PIK3CA mutation

The next Virtual Molecular Tumor Board
Hosted by Dr. Lee Schwartzberg
West Cancer Center
Date: Tuesday February 23, 2016
Please direct questions regarding the VMTB to
cariscentersofexcellence@carisls.com
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Caris Centers of Excellence Virtual Molecular Tumor Board Fox Chase - Jan 26, 2016 (No Audio)

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