1. health and fitness
2. disease
3. cancer

PAGE 1 of 14
SPECIMEN INFORMATION
Patient Name
ORDERED BY
Ordering Physician Name
The Cancer Center
Primary Tumor Site: Upper lobe, lung
Specimen Site: Upper lobe, lung
Specimen Collected: XX/XX/2013
Specimen Received: XX/XX/2013
Initiation of Testing: XX/XX/2013
Completion of Testing: XX/XX/2013
Specimen Id: XYZ-123
1234 Main Street
Dallas, TX 12345
(123) 456-7890
SE
U
AL
Case Number: TN13-111111
Date Of Birth: XX/XX/1942
Sex: Female
.
PATIENT
Agents Associated with
Potential BENEFIT
Potential Targets
Associated
with CLINICAL TRIALS
FO
R
Agents Associated With
Potential LACK OF BENEFIT
.N
O
gemcitabine
erlotinib
N
LY
paclitaxel, docetaxel, nabpaclitaxel
pemetrexed
cMET
T
crizotinib
TM
ON NCCN COMPENDIUM
MI-2013-10-10.0
C
LI
N
IC
Molecular Intelligence Summary
cetuximab
O
trastuzumab, pertuzumab,
ado-trastuzumab emtansine
(T-DM1)
lapatinib
TM
PU
R
gefitinib
PO
OFF NCCN COMPENDIUM
SE
S
irinotecan
E
fluorouracil, capecitabine
R
ST
temozolomide, dacarbazine
AT
IV
doxorubicin, liposomaldoxorubicin, epirubicin
LU
afatinib
SA
M
PL
E
R
EP
O
R
T.
IL
Presence of T790M mutation in EGFR has been associated with higher likelihood of prolonged efficacy (PFS/OS) with afatinib than gefitinib
or erlotinib (Katakami, et al. 2013). Recent data including AMP, CAP and NCCN guidelines support the continued use of EGFR TKIs in lung
adenocarcinoma patients with EGFR activating mutations after the acquisition of a secondary mutation in EGFR-T790M that renders the
kinase resistant to erlotinib or gefitinib. To overcome resistance, EGFR should continue to be targeted and discontinuation of EGFR TKIs may
lead to further progression of the disease. (Lindeman, et al. 2013).
Agents associated with potential benefit or lack of benefit, as indicated above, are based on biomarker results provided in this report, and
are based on published medical evidence. This evidence may have been obtained from the studies performed in the cancer type present in
the tested patient's sample or derived from another tumor type.
The selection of any, all or none of the matched agents resides solely with the discretion of the treating physician. Decisions on patient care and treatment must
be based on the independent medical judgment of the treating physician, taking into consideration all applicable information concerning the patient’s condition,
such as patient and family history, physical examinations, information from other diagnostic tests, and patient preferences, in accordance with the applicable
standard of care. Decisions regarding care and treatment should not be based on a single test such as this test or the information contained in this report.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
TN1014
PAGE 2 of 14
Clinical History
.
Per the submitted surgical pathology report (XYZ-123), the patient is a 71 year-old female with a history of adenocarcinoma.
IC
AL
U
SE
Submitted Pathologic Diagnosis
Lung, right upper lobe mass, wedge resection: Two separate foci of moderately differentiated adenocarcinoma with acinar and papillary
patterns.
The specimens consist of:
SA
M
PL
E
R
EP
O
R
T.
IL
LU
ST
R
AT
IV
E
PU
R
PO
SE
S
O
N
LY
.N
O
T
FO
R
C
1 (A) Paraffin Block - Client ID (XYZ-123), with the corresponding surgical pathology report labeled "XYZ-123".
LI
N
Specimens Received (Gross Description)
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 3 of 14
Agents Associated with Potential BENEFIT
cMET
CISH
Not Amplified
2.40
✔
EGFR
Next
Gen SEQ
Pathogenic
L858R
✔
EGFR
T790M
Next
Gen SEQ
Pathogenic
T790M
KRAS
Next
Gen SEQ
Wild Type
PIK3CA
Next
Gen SEQ
Wild Type
PTEN
IHC
Positive
2+ 60%
TS
IHC
Negative
cetuximab
EGFR
IHC HScore
Positive
irinotecan
TOPO1
IHC
Positive
Her2/Neu
CISH
PGP
IHC
✝
Decreased
Potential
Benefit
Data
Reference
Level*
LI
N
C
FO
R
.N
O
T
✔
✔
.
Lack of
Potential
Benefit
IC
Potential
Benefit
2, 4
9, 11,
12, 13
5, 6, 7, 8
9, 10
2, 3
✔
1
✔
20, 21, 22
298
✔
24
2+ 30%
✔
34, 35, 36
N
LY
✔
S
erlotinib, gefitinib
Value
SE
Result
U
Method
O
Agents
AL
Test
SE
Clinical Association
temozolomide,
dacarbazine
PO
R
PU
E
Negative
0+ 100%
✔
37, 38
IHC
Positive
2+ 20%
✔
41, 42
IHC
Negative
1+ 20%
✔
43, 44
✔
39, 40
SA
M
PL
E
R
EP
O
R
T.
MGMT
IV
AT
1.21
R
IL
TOP2A
1+ 7%
Not Amplified
LU
doxorubicin,
liposomaldoxorubicin,
epirubicin
ST
fluorouracil,
capecitabine,
pemetrexed
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 4 of 14
Agents Associated with Potential BENEFIT
Next
Gen SEQ
Pathogenic
L858R
EGFR
T790M
Next
Gen SEQ
Pathogenic
T790M
Decreased
Potential
Benefit
Lack of
Potential
Benefit
Data
Reference
Level*
IC
Potential
Benefit
SE
EGFR
✝
Value
U
Result
AL
Method
LI
N
✔
✔
C
afatinib
Test
50
50
FO
R
Agents
.
Clinical Association
.N
O
T
*The level of evidence for all references is assigned according to the Literature Level of Evidence Framework consistent with the US Preventive
Services Task Force described further in the Appendix of this report. The data level of each biomarker-drug interaction is the average level
of evidence based on the body of evidence, overall clinical utility, competing biomarker interactions and tumor type from which the evidence
was gathered.
LY
= Greater level of evidence
N
= Intermediate level of evidence
S
O
= Lower level of evidence
SA
M
PL
E
R
EP
O
R
T.
IL
LU
ST
R
AT
IV
E
PU
R
PO
SE
✝ Refer to Appendix for detailed Result and Value information for each biomarker, including appropriate cutoffs, unit of measure, etc.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 5 of 14
Agents Associated with Potential LACK OF BENEFIT
FISH
Negative
ROS1
FISH
Negative
RRM1
IHC
Positive
2+ 50%
PGP
IHC
Negative
0+ 100%
SPARC
Monoclonal
IHC
Negative
1+ 80%
SPARC
Polyclonal
IHC
Negative
1+ 25%
TLE3
IHC
Negative
TUBB3
IHC
Positive
Her2/Neu
CISH
Not Amplified
Her2/Neu
IHC
LI
N
23
FO
R
C
✔
.N
O
T
30, 31
✔
✔
32, 33
0+ 100%
✔
28, 29
3+ 95%
✔
25, 26, 27
1.21
✔
52, 53,
54, 55, 56,
57, 58, 59
Negative
0+ 100%
✔
52, 53,
54, 55,
56, 57, 58
Not Amplified
1.21
✔
59, 60,
61, 62
Negative
0+ 100%
✔
60, 61, 62
O
N
LY
32, 33
PU
IV
AT
R
CISH
LU
lapatinib
ST
Her2/Neu
IHC
R
T.
IL
Her2/Neu
14, 15
16, 17,
18, 19
E
trastuzumab,
pertuzumab, adotrastuzumab
emtansine (T-DM1)
Data
Reference
Level*
✔
R
paclitaxel,
docetaxel, nabpaclitaxel
Lack of
Potential
Benefit
✔
S
gemcitabine
Decreased
Potential
Benefit
✔
SE
crizotinib
Potential
Benefit
SE
ALK
✝
Value
U
Result
AL
Method
IC
Test
PO
Agents
.
Clinical Association
R
EP
O
*The level of evidence for all references is assigned according to the Literature Level of Evidence Framework consistent with the US Preventive
Services Task Force described further in the Appendix of this report. The data level of each biomarker-drug interaction is the average level
of evidence based on the body of evidence, overall clinical utility, competing biomarker interactions and tumor type from which the evidence
was gathered.
M
PL
E
= Greater level of evidence
= Intermediate level of evidence
SA
= Lower level of evidence
✝ Refer to Appendix for detailed Result and Value information for each biomarker, including appropriate cutoffs, unit of measure, etc.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 6 of 14
Agents Associated with INDETERMINATE BENEFIT
Wild Type
RET
Next
Gen SEQ
Wild Type
PIK3CA
Next
Gen SEQ
Wild Type
45, 46
47, 48, 49
51
✔
63, 64, 65
LY
everolimus,
temsirolimus
✔
O
vandetanib
SE
Next
Gen SEQ
✔
Data
Reference
Level*
U
PDGFRA
imatinib
Lack of
Potential
Benefit
AL
Wild Type
Decreased
Potential
Benefit
IC
Next
Gen SEQ
Potential
Benefit
LI
N
c-KIT
✝
Value
C
Result
FO
R
Method
T
Test
.N
Agents
.
Clinical Association
SE
S
O
N
*The level of evidence for all references is assigned according to the Literature Level of Evidence Framework consistent with the US Preventive
Services Task Force described further in the Appendix of this report. The data level of each biomarker-drug interaction is the average level
of evidence based on the body of evidence, overall clinical utility, competing biomarker interactions and tumor type from which the evidence
was gathered.
PO
= Greater level of evidence
R
= Intermediate level of evidence
PU
= Lower level of evidence
SA
M
PL
E
R
EP
O
R
T.
IL
LU
ST
R
AT
IV
E
✝ Refer to Appendix for detailed Result and Value information for each biomarker, including appropriate cutoffs, unit of measure, etc.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 7 of 14
SE
.
Expanded Mutational Analysis by Next Generation Sequencing
Frequency (%)
Exon
EGFR
L858R
74
21
Result
IC
Alteration
Pathogenic
LI
N
Gene
AL
U
Genes Tested With Alterations
C
Interpretation: A pathogenic mutation was detected in EGFR
O
N
LY
.N
O
T
FO
R
EGFR or epidermal growth factor receptor, is a transmembrane receptor tyrosine kinase belonging to the ErbB family of receptors.
Upon ligand binding, the activated receptor triggers a series of intracellular pathways (Ras/MAPK, PI3K/Akt, JAK-STAT) that result in cell
proliferation, migration and adhesion. Dysregulation of EGFR through mutation leads to ligand-independent activation and constitutive
kinase activity, which results in uncontrolled growth and proliferation of many human cancers. EGFR mutations have been observed in
20-25% of non-small cell lung cancer (NSCLC), 10% of endometrial and peritoneal cancers. Somatic gain-of-function EGFR mutations,
including in-frame deletions in exon 19 or point mutations in exon 21, confer sensitivity to first- and second-generation tyrosine kinase
inhibitors (TKIs), whereas the secondary mutation, T790M in exon 20, confers reduced response. New agents and novel combination
therapies are being explored (www.clinicaltrials.gov) for primary treatment of EGFR-mutated patients, as well as for patients that
have progressed, including second-generation TKIs such as icotinib (NCT01665417) or combination therapies that include afatinib
(NCT01647711) for NSCLC.
T790M
23
SE
EGFR
S
Germline mutations and polymorphisms of EGFR have been associated with familial lung adenocarcinomas.
20
Pathogenic
PU
R
PO
Interpretation: Presence of the T790M mutation has been associated with acquired resistance to EGFR-targeted tyrosine kinase inhibitors,
therefore erlotinib and gefitinib are potentially of minimal benefit for this patient. However, recent data including NCCN guidelines support the
continued use of EGFR TKIs in lung adenocarcinoma patients with EGFR activating mutations after the acquisition of a secondary mutation
in EGFR-T790M that renders the kinase resistant to erlotinib and gefitinib. To overcome resistance, EGFR should continue to be targeted
and discontinuation of EGFR TKIs may lead to further progression of the disease. A second generation EGFR TKI may also be considered.
R
T.
IL
LU
ST
R
AT
IV
E
EGFR or epidermal growth factor receptor, is a transmembrane receptor tyrosine kinase belonging to the ErbB family of receptors.
Upon ligand binding, the activated receptor triggers a series of intracellular pathways (Ras/MAPK, PI3K/Akt, JAK-STAT) that result in cell
proliferation, migration and adhesion. Dysregulation of EGFR through mutation leads to ligand-independent activation and constitutive
kinase activity, which results in uncontrolled growth and proliferation of many human cancers. EGFR mutations have been observed in
20-25% of non-small cell lung cancer (NSCLC), 10% of endometrial and peritoneal cancers. Somatic gain-of-function EGFR mutations,
including in-frame deletions in exon 19 or point mutations in exon 21, confer sensitivity to first- and second-generation tyrosine kinase
inhibitors (TKIs), whereas the secondary mutation, T790M in exon 20, confers reduced response. New agents and novel combination
therapies are being explored (www.clinicaltrials.gov) for primary treatment of EGFR-mutated patients, as well as for patients that
have progressed, including second-generation TKIs such as icotinib (NCT01665417) or combination therapies that include afatinib
(NCT01647711) for NSCLC.
SA
M
PL
E
R
EP
O
Germline mutations and polymorphisms of EGFR have been associated with familial lung adenocarcinomas.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 8 of 14
Genes Tested With Alterations
Alteration
Frequency (%)
Exon
Result
TP53
Y236H
14
7
Presumed Pathogenic
U
SE
.
Gene
IC
AL
Interpretation: A TP53 mutation was detected in this sample. This mutation has been reported previously for several tumor types in limited
publications. Despite these reports, The clinical significance of this mutation is not fully known and therefore is classified as Presumed
Pathogenic.
.N
O
T
FO
R
C
LI
N
TP53, or p53, plays a central role in modulating response to cellular stress through transcriptional regulation of genes involved in cellcycle arrest, DNA repair, apoptosis, and senescence. Inactivation of the p53 pathway is essential for the formation of the majority of human
tumors. Mutation in p53 (TP53) remains one of the most commonly described genetic events in human neoplasia, estimated to occur in
30-50% of all cancers with the highest mutation rates occurring in head and neck squamous cell carcinoma and colorectal cancer. Generally,
presence of a disruptive p53 mutation is associated with a poor prognosis in all types of cancers, and diminished sensitivity to radiation
and chemotherapy. In addition, various clinical trials (on www.clinicaltrials.gov) investigating agents which target p53's downstream or
upstream effectors may have clinical utility depending on the p53 status. For p53 mutated patients, Chk1 inhibitors in advanced cancer
(NCT01115790) and Wee1 inhibitors in ovarian cancer (NCT01164995, NCT01357161) are being investigated. For p53 wildtype patients
with sarcoma, mdm2 inhibitors (NCT01605526) are being investigated.
S
O
N
LY
Germline p53 mutations are associated with the Li-Fraumeni syndrome (LFS) which may lead to early-onset of several forms of cancer
currently known to occur in the syndrome, including sarcomas of the bone and soft tissues, carcinomas of the breast and adrenal cortex
(hereditary adrenocortical carcinoma), brain tumors and acute leukemias.
PO
APC
CSF1R
FGFR2
IDH1
MPL
ATM
CTNNB1
FLT3
JAK2
NOTCH1
BRAF
ERBB2
GNA11
PTEN
RET
Electronic Signature
SA
M
PL
E
R
EP
O
R
T.
IL
LU
ST
R
AT
IV
E
ALK
cMET
FGFR1
HRAS
PIK3CA
R
AKT1
KRAS
GNAQ
PDGFRA
MLH1
VHL
PU
ABL1
c-KIT
GNAS
KDR
NRAS
SMO
SE
Genes Tested Without Alterations
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
PAGE 9 of 14
TM
Clinical Trials Connector
Locations
AL, AZ, CA, CO, FL,
GA, IL, IN, LA, MA, MN,
MO, NV, NC, OH, OR,
PA, WA
.
Drug(s)
SE
Potential
Target
Phase
U
Title
2
cMET
onartuzumab
NCT01496742
A Study of Onartuzumab (MetMAb) in
Combination With Bevacizumab (Avastin) Plus
Platinum And Paclitaxel or With Pemetrexed
Plus Platinum in Patients With Non-Squamous
Non-Small Cell Lung Cancer
2
cMET
onartuzumab
NCT01395758
Erlotinib Plus ARQ 197 Versus Single Agent
Chemotherapy in Locally Advanced or
Metastatic Non-Small Cell Lung Cancer
2
cMET
NCT01121575
A Study Of Combined C- MET Inhibitor
And PAN-HER Inhibitor (PF-02341066 And
PF-00299804) In Patients With Non- Small
Cell Lung Cancer
1
NCT01014936
First-in-Man, Dose-escalation Trial of C-met
Kinase Inhibitor EMD 1214063 in Subjects
With Advanced Solid Tumors
LI
N
IC
NCT01519804
A Study of Onartuzumab (MetMAb) Versus
Placebo in Combination With Paclitaxel Plus
Platinum in Patients With Squamous NonSmall Cell Lung Cancer
AL
Protocol
T
FO
R
C
AL, AZ, CA, CO, FL,
GA, IL, IN, LA, NV, NY,
NC, OH, OR, PA, WA
CA, CO, DC, FL, IL, KS,
MD, MA, PA, SC, TX
cMET
crizotinib
CO, MD, MA
cMET
EMD 1214063
SE
S
O
N
LY
.N
O
ARQ 197
TX
SA
M
PL
E
R
EP
O
R
T.
IL
LU
ST
R
AT
IV
E
PU
R
PO
1
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
To view the rest of the report, contact a
Molecular Intelligence representative today.
(888) 979-8669
[email protected]
** FINAL REPORT **
Patient: Patient Report
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences