Slide deck from Caris Life Sciences' Virtual Molecular Tumor Board hosted by the COE Network.

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Patient 1

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Clinical History
• male, early 50's, metastatic CRC
• 2 years ago, presented with near obstructing sigmoid cancer, large
volume liver mets, increased LFTs
• KRAS/extended RAS WT from SC node biopsy
• Treated with XELOX + Bev- strong PR
• Cardiac event- changed to bolus 5FU/bev maintenance
• PD 12 months ago- changed to IRI + Panitumumab– PR, rash
• CEA increased- increased bowel symptoms-
• CT showed only PD in colon primary- partial obstruction
• Surgical resection of primary
• KRAS mutation on CARIS profile
• PD while off chemo during surgery, retreated with IRI + Panitumumab,
responding again

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Caris Molecular Intelligence Profile
Test One: at diagnosis

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Caris Molecular Intelligence Profile
Test One: at diagnosis
pan-RAS testing: QNS, thus no cetuximab treatment association

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Relevant Stains
• specimen 1 (2014) specimen 2 (2015)

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Caris Molecular Intelligence Profile
Test Two: 2 months later

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Caris Molecular Intelligence Profile
Test Two: 2 months later

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Caris Molecular Intelligence Profile
Test Two: 2 months later

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Molecular Tumor Summary
• KRAS
• previous LN KRAS WT
• First Caris specimen QNS
• Repeat Caris test: K-RAS exon2 G12V mutation
• BRCA1 and BRCA2 VUS
• Not clinically actionable
• Predicted beneficial cytotoxics:
• 5-FU / Capecitabine
• Irinotecan
• Taxanes

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Discussion Points
•KRAS mutated primary, mets WT
•What next?
•BRCA mutations?

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Patient 2

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Treatment Summary
• male, early 50's, met CRC
– Refractory to Oxali, irinotecan
• KRAS mut
• Enrolled on regorafanib trial
– Biopsy at baseline and on treatment for
biomarker discovery
– Currently responding

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Caris report
• QNS
– Discuss tissue sample needs for analysis and trials

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Caris Molecular Intelligence Profile
Initial testing at diagnosis

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Caris Molecular Intelligence Profile
Repeat testing

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Relevant Stains
• first specimen
(2014) second specimen (2015)

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Relevant Stains
• 2014: TOPO1
2+/15%, patchy 2015: TOPO1 2+/100% limited
sample size and bias

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Molecular Tumor Summary
• Initial testing:
• KRAS mutation G12D, exon 2
• PD-1 positive IHC, PD-L1 negative
• APC mutation S1362fs
• CMET mutation T1010I
• Subsequent testing (IHC only):
• TOPO1 positive / irinotecan beneficial
• TS positive / 5-FU & Cape non-beneficial

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Patient 3

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Clinical History
• female, early 40's, previously healthy
• Developed fatigue and iron deficiency
• Back pain
• CT abdomen revealed:
– Acending colon lesion 3.6 cm
– Liver radiodensities up to 3.2 x 2.6cm

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Pathology
• Metastatic colorectal adenocarcinoma
• KRAS codon 12 mutation in exon 2 detected

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Clinical Course
• Started on XELOX + Bevacizumab
• Required dose reduction in Xeloda and Oxaliplatin due
to severe fatigue
• Achieved stable disease
• Followed by maintenance Xeloda + Bevacizumab
• Developed abdominal pain 5 months after initial diagnosis
• CT revealed free air, suspicious for perforation
• CEA elevation to 369
• Resumed XELOX
• Developed oxaliplatin allergy
• Changed to Xeloda single agent
• Non-obstructive hyperbilirubinemia (direct bili. 6.5)
• No irinotecan

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Caris Molecular Intelligence Profile

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Caris IHC Findings

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Relevant Stains
• H & E MSH2

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Relevant Stains
• TOPO1 TS

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Relevant Stains
• PD-1 PD-L1

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Caris Molecular Intelligence Profile

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Tumor Profile Summary
• KRAS exon 2 mutation G13D (no anti-EGFR)
• cMET mutation T1010I (clinical trial options)
• PD-1 expression (clinical trial options)
• Low TS expression (capecitabine benefit)
• TOPO1 overexpression (irinotecan benefit)
• MSI-normal, normal MLH1/MSH2

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Patient 4

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Clinical History
• Demographics: male, mid-30's
Relevant medical history:
• Non-corrected undescended testes
• Initial diagnosis – RP mass – Mixed germ cell tumor
• Recurrent disease- at 6 months, one year, four years, seven
years, and nine years
• Most recent recurrence- HTN, decreased renal function due
to renal artery compression by tumor. Renal artery stent with
improvement in kidney function
• Symptoms / physical findings:
– abdominal pain, weight loss, HTN

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Prior Treatment
Initial diagnosis: PEB X 4 followed by incomplete
resection of retroperitoneal disease
At 6 months: TIP X 2 followed by triple tandem PSCT
At 1 year: Resection of residual mass-teratoma
At 4 years: Recurrent abdominal disease
resected/ nephrectomy- teratoma
At 7 years: Mass in pancreas
resected, splenectomy- GCT
At 9 years: Recurrent intra abdominal disease- GCT
EP X 4 followed by resection followed by EP X2

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Radiology
• Most recent recurrence:
• CT scan abdomen
– increased nodularity in the mesentery,
• PET scan
– 2 areas of increased uptake retroperitoneum
• Renal artery compression by tumor

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Pathology
• Initial diagnosis: RP mass- embryonal,
choriocarcinoma, yolk sac, mature teratoma
• At one year: Teratoma
• At four years: Teratoma
• At 7 years: Embryonal, yolk sac, teratoma
• At 9 years: Metastatic carcinoma c/w GCT
showing features of embryonal carcinoma

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Caris Molecular Intelligence Profile

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Caris Molecular Intelligence Profile

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Relevant Stains
• H&E: Yolk sac
component EGFR (L718R 97%): 1+/70% total
EGFR expression (IHC)

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Molecular Tumor Summary
• Standard first-line BEP treatment has no established
biomarker specific for germ cell tumor lineage
• Second-line therapies with biomarkers include taxanes
and gemcitabine
• Molecular profiling favors taxanes over gemcitabine
• Off-label considerations of potential benefit include
anthracyclines and temozolomide