SPECIMEN INFORMATION Ordering Physician Name The Cancer Center 1234 Main Street Dallas, TX 12345 (123) 456-7890 IC AL Primary Tumor Site: Ovary Specimen Site: Ovary Specimen Collected: XX/XX/2013 Specimen Received: XX/XX/2013 Initiation of Testing: 1/16/2013 Completion of Testing: Specimen Id: XYZ-123 Case Number: TN13-111111 Date Of Birth: XX/XX/1960 Sex: Female SE . Patient Name ORDERED BY U PATIENT Agents Associated with Potential BENEFIT FO R C LI N Molecular Intelligence Ovarian Surface Epithelial Carcinoma Comprehensive PLUS NGS Panel Summary O N LY . docetaxel, paclitaxel TM ON NCCN COMPENDIUM cisplatin, carboplatin N irinotecan, topotecan Potential Targets Associated with CLINICAL TRIALS T Agents Associated With Potential LACK OF BENEFIT BRAF KRAS liposomal-doxorubicin everolimus, temsirolimus GNA11 leuprolide, megestrol acetate nab-paclitaxel Her2/Neu capecitabine, pemetrexed temozolomide, dacarbazine PU imatinib cMET R PO SE S O gemcitabine tamoxifen, fulvestrant, letrozole, anastrozole TM sunitinib E OFF NCCN COMPENDIUM MI-2013-01-26.0 doxorubicin, epirubicin IV vemurafenib AT fluorouracil IL LU ST R trastuzumab SA M PL E R EP O R T. 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 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 Clinical History SE . 53 year old woman with ovarian carcinoma IC AL U Submitted Pathologic Diagnosis Serous Carcinoma LI N Specimens Received (Gross Description) The specimens consist of: FO R C 1 (A) Tissue Biopsy Formalin Vial - Client ID (XYZ-123). Interpretation (Caris Life Sciences Microscopic Diagnosis): N O T Ovarian carcinoma LY . Electronic Signature PO SE S O N By my electronic signature, I as the attending pathologist affirm that I have personally reviewed and examined microscopically the prepared slide(s) and that the above diagnosis has been made or confirmed by me. R Disclaimer IV E PU All of the individual assays that are available through Caris Life Sciences® Molecular Intelligence™ Services (Caris Molecular Intelligence) were developed and validated by Caris MPI, Inc. d/b/a Caris Life Sciences and their test performance characteristics were determined and validated by Caris Life Sciences pursuant to the Clinical Laboratory Improvements Amendments and accompanying regulations ("CLIA"). Some of the assays that are part of Caris Molecular Intelligence have been cleared or approved by the U.S. Food and Drug Administration (FDA). The clinical reference laboratory of Caris MPI, Inc. is certified under CLIA to perform high complexity testing, including all of the assays that are part of the Caris Molecular Intelligence. LU ST R AT The CLIA certification number of each Caris MPI, Inc. laboratory performing testing in connection with Caris Molecular Intelligence can be found at the bottom of each page. This Report includes information about therapeutic agents that appear to be associated with clinical benefit based on NCCN Compendium guidelines, relevance of tumor lineage, level of published evidence and strength of biomarker expression, as available, reviewed and assessed by Caris Life Sciences. The agents are not ranked in order of potential or predicted efficacy. The finding of a biomarker expression does not necessarily indicate pharmacologic effectiveness or lack thereof. The agents identified may or may not be suitable for use with a particular patient and the report does not guarantee or suggest that any particular agent will be effective with the treatment of any particular condition. Caris Life Sciences expressly disclaims and makes no representation or warranty whatsoever relating, directly or indirectly, to this review of evidence or identified scientific literature, the conclusions drawn from it or any of the information set forth in this Report that is derived from such review, including information and conclusions relating to therapeutic agents that are included or omitted from this Report. T. IL The decision to select 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. R EP O R The information presented in the Clinical Trials Connector™ section of the Report is compiled from sources believed to be reliable and current. We have used our best efforts to make this information as accurate as possible. However, the accuracy and completeness of this information cannot be guaranteed. The contents are to be used for clinical trial guidance and may not include all relevant trials. Current enrollment status for these trials is unknown. The clinical trials information present in the biomarker description was compiled from www.clinicaltrials.gov. The contents are to be used only as a guide, and health care providers should employ clinical judgment in interpreting this information for individual patients. Specific entrance criteria for each clinical trial should be reviewed as additional inclusion criteria may apply. Caris Life Sciences makes no promises or guarantees that a healthcare provider, insurer or other third party payor, whether private or governmental, will provide reimbursement (instead of coverage) for any of the tests performed. SA M PL E The next generation sequencing assay performed by Caris Life Sciences examines tumor tissue only and does not examine normal tissues such as tumor adjacent tissue or whole/ peripheral blood. As such, the origin of any mutation detected by our assay may either be a somatic (not inherited) or a germline mutation (inherited) and will not be distinguishable by this assay. It is recommended that results be considered within the clinical context and history of the patient. If a germline inheritance pattern is suspected then counseling by a board certified genetic counselor is recommended. ** 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 SE . Agents Associated with Potential BENEFIT Data Reference Level* Method Result Value cisplatin, carboplatin ERCC1 IHC Negative 2+ 20% ✔ gemcitabine RRM1 IHC Negative 1+ 30% ✔ Her2/Neu CISH Amplified 2.40 ✔ PGP IHC Positive 1+ 30% TOP2A FISH Not Amplified 1.33 ER IHC Negative 1+ 20% PR IHC Positive 1+ 20% ✔ 22, 23 TS IHC Negative 1+ 5% ✔ 25, 26, 27 Her2/Neu CISH Amplified 2.40 ✔ 33, 34 Her2/Neu IHC 3+ 20% ✔ 35 Decreased Potential Benefit Lack of Potential Benefit LI N Potential Benefit IC ✝ AL Test 1, 2 10 11, 12 13, 14 ✔ 11, 15, 16, 17 ✔ 22, 23, 24 S O N LY . N ✔ E IV Positive AT trastuzumab PU R fluorouracil, capecitabine, pemetrexed PO SE leuprolide, megestrol acetate O T doxorubicin, liposomaldoxorubicin, epirubicin FO R C Agents U Clinical Association = Greater level of evidence LU ST R *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. IL = Intermediate level of evidence R T. = Lower level of evidence SA M PL E R EP O ✝ Refer to Appendix for detailed Result and Value information for each biomarker, including appropriate cutoffs, unit of measure, etc. ** 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 SE . Agents Associated with Potential LACK OF BENEFIT Result Value PGP IHC Positive 1+ 30% TUBB3 IHC Positive 2+ 30% irinotecan, topotecan TOPO1 IHC Negative 2+ 20% tamoxifen, fulvestrant, letrozole, anastrozole ER IHC Negative 1+ 20% PIK3CA Next Gen SEQ Presumed Pathogenic G1007R PTEN IHC Positive SPARC Monoclonal IHC Negative SPARC Polyclonal IHC Negative MGMT IHC c-KIT Next Gen SEQ Decreased Potential Benefit Lack of Potential Benefit Data Reference Level* LI N Potential Benefit C ✔ 3, 4 ✔ 5, 6 ✔ 7, 8, 9 ✔ 18, 19, 20, 21 2+ 60% ✔ 28, 29, 30 0+ 100% ✔ 31, 32 1+ 20% ✔ 31, 32 1+ 50% ✔ 36, 37 Wild Type ✔ 41, 42, 43 Next Gen SEQ Wild Type ✔ 38, 39, 40 Next Gen SEQ Wild Type ✔ 41, 42, 43 imatinib IL c-KIT E IV LY . N O S PO SE SA M PL E R EP O R T. sunitinib PU R LU PDGFRA Positive AT temozolomide, dacarbazine R nab-paclitaxel ST everolimus, temsirolimus N O T docetaxel, paclitaxel ✝ AL Method IC Test FO R Agents U Clinical Association ** 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 U SE . Expanded Mutational Analysis by Next Generation Sequencing Frequency (%) Exon APC E1353X 59 16 Result LI N Alteration Pathogenic C Gene IC AL Genes Tested With Alterations FO R Interpretation: A nonsense variant was detected in this sample. S O N LY . N O T APC or adenomatous polyposis coli is a key tumor suppressor gene that encodes for a large multi-domain protein. This protein exerts its tumor suppressor function in the Wnt/b-catenin cascade mainly by controlling the degradation of b-catenin, the central activator of transcription in the Wnt signaling pathway. The Wnt signaling pathway mediates important cellular functions including intercellular adhesion, stabilization of the cytoskeleton, and cell cycle regulation and apoptosis, and it is important in embryonic development and oncogenesis. Mutation in APC results in a truncated protein product with abnormal function, lacking the domains involved in b-catenin degradation. Somatic mutation in the APC gene can be detected in the majority of colorectal tumors (80%) and it is an early event in colorectal tumorigenesis. APC wild type patients have shown better disease control rate in the metastatic setting when treated with oxaliplatin, while when treated with fluoropyrimidine regimens, APC wild type patients experience more hematological toxicities. APC mutation has also been identified in oral squamous cell carcinoma, gastric cancer as well as hepatoblastoma and may contribute to cancer formation. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene and/or its downstream or upstream effectors maybe available, which include the following: NCT01351103. BRAF PU R PO SE Germline mutation in APC causes familial adenomatous polyposis, which is an autosomal dominant inherited disease that will inevitably develop to colorectal cancer if left untreated. COX-2 inhibitors including celecoxib may reduce the recurrence of adenomas and incidence of advanced adenomas in individuals with an increased risk of CRC. Turcot syndrome and Gardner's syndrome have also been associated with germline APC defects. Germline mutations of the APC have also been associated with an increased risk of developing desmoid disease, papillary thyroid carcinoma and hepatoblastoma. G464E 55 33 Pathogenic E Interpretation: A pathogenic variant was detected in this sample. LU ST R AT IV BRAF encodes a protein belonging to the raf/mil family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway initiated by EGFR activation, which affects cell division, differentiation, and secretion. BRAF somatic mutations have been found in melanoma (43%), thyroid (39%), biliary tree (14%), colon (12%), and ovarian tumors (12%). Patients with mutated BRAF genes have a reduced likelihood of response to EGFR targeted monoclonal antibodies, such as cetuximab in colorectal cancer. A BRAF enzyme inhibitor, vemurafenib, was approved by FDA to treat unresectable or metastatic melanoma patients harboring BRAF V600E mutations. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene may be available, which include the following: NCT01543698, NCT01352273, NCT01709292. R GNA11 T. IL BRAF inherited mutations are associated with Noonan/Cardio-Facio-Cutaneous (CFC) syndrome, syndromes associated with short stature, distinct facial features, and potential heart/skeletal abnormalities. Q209L 43 4 Pathogenic EP O Interpretation: A pathogenic variant was detected in this sample. SA M PL E R GNA11 is a proto-oncogene that belongs to the Gq family of the G alpha family of G protein coupled receptors. Known downstream signaling partners of GNA11 are phospholipase C beta and RhoA and activation of GNA11 induces MAPK activity. Over half of uveal melanoma patients lacking a mutation in GNAQ exhibit somatic mutations in GNA11. Activating mutations of GNA11 have not been found in other malignancies. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene may be available, which include the following: NCT01587352, NCT01390818, NCT01143402. ** 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 Frequency (%) Exon Result G12D 50 18 Pathogenic SE . Alteration KRAS AL Gene U Genes Tested With Alterations IC Interpretation: A pathogenic variant was detected in this sample. FO R C LI N KRAS or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog encodes a signaling intermediate involved in many signaling cascades including the EGFR pathway. KRAS somatic mutations have been found in pancreatic (57%), colon (35%), lung (16%), biliary tract (28%), and endometrial (15%) cancers. Mutations at activating hotspots are associated with resistance to EGFR tyrosine kinase inhibitors (erlotinib, gefitinib) and monoclonal antibodies (cetuximab, panitumumab). Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene may be available, which include the following: NCT01248247, NCT01229150. Several germline mutations of KRAS (V14I, T58I, and D153V amino acid substitutions) are associated with Noonan syndrome. 25 2 T G1007R O PIK3CA Presumed Pathogenic LY . N Interpretation: A variant of unknown clinical significance was detected in this sample. However, this variant has been detected in more than 5 cancer samples increasing the likelihood that this is a pathogenic mutation. PO SE S O N PIK3CA or phosphoinositide-3-kinase catalytic alpha polypeptide encodes a protein in the PI3 kinase pathway. This pathway is an active target for drug development. PIK3CA somatic mutations have been found in breast (26%), endometrial (23%), urinary tract (19%), colon (13%), and ovarian (11%) cancers. Somatic mosaic activating mutations in PIK3CA are said to cause CLOVES syndrome. PIK3CA mutations have been associated with benefit from mTOR inhibitors (everolimus, temsirolimus). Evidence suggests that breast cancer patients with activation of the PI3K pathway due to PTEN loss or PIK3CA mutation have a significantly shorter survival following trastuzumab treatment. PIK3CA mutated colorectal cancer patients are less likely to respond to EGFR targeted monoclonal antibody therapy. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene may be available, which include the following: NCT00877773, NCT01277757, NCT01219699. PU ALK CTNNB1 FGFR2 JAK2 NPM1 RET VHL R AT IV E AKT1 CSF1R FGFR1 IDH1 NOTCH1 RB1 TP53 ATM EGFR FLT3 JAK3 NRAS SMAD4 c-KIT ERBB2 GNAS KDR PDGFRA SMARCB1 CDH1 ERBB4 HNF1A MLH1 PTEN SMO SA M PL E R EP O R T. IL LU ST ABL1 cMET FBXW7 HRAS MPL PTPN11 STK11 R Genes Tested Without Alterations ** 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 Title Phase Potential Target Drug(s) NCT01543698 A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors 1 BRAF , KRAS MEK162 NCT01531361 Vemurafenib and Sorafenib in Advanced Cancer 1 BRAF sorafenib , vemurafenib C NCT01517399 Drug-drug Interaction Study of Tivantinib (ARQ 197) With Omeprazole, S-warfarin, Caffeine, Midazolam, and Digoxin in Cancer Subjects 1 cMET ARQ 197 TX NCT01468922 Pazopanib and ARQ 197 for Advanced Solid Tumors 1 cMET NCT01450384 Pemetrexed Disodium and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors 1 BRAF NCT01449058 A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors 1|2 NCT01392521 Phase Ib Study of PI3(Phosphoinositol 3)Kinase Inhibitor BAY80-6946 With MEK (Mitogen-activated Protein Kinase) Inhibitor BAY86-9766 in Patients With Advanced Cancer NCT01390818 Trial of MEK Inhibitor and PI3K/mTOR Inhibitor in Subjects With Locally Advanced or Metastatic Solid Tumors NCT01376310 NCT01363232 IC AL U Locations LI N MA, TX T FO R TX O N Protocol SE . TM Clinical Trials Connector MD sorafenib VA BRAF , KRAS BYL719 MA, UT 1 BRAF , KRAS Bay 86-9766 AZ, TX 1 GNA11 GSK1120212 Rollover Study 2 BRAF , KRAS GSK1120212 Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients 1 BRAF , KRAS MEK162 MA, MI, NY, SC MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations 1 KRAS MEK162 FL, OR, UT Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients 1 BRAF , KRAS MEK162 MA, TX, WI Sorafenib Tosylate and Stereotactic Radiosurgery in Treating Patients With Brain Metastases 1 BRAF sorafenib TN MSC1936369B , SAR245409 MA, TN (XL-765) AZ, CO, MI, NH, PA, TN, TX, WA EP O R T. IL LU ST R AT IV E PU R PO SE S O N LY . ARQ 197 E R NCT01352273 SA M PL NCT01337765 NCT01276210 ** 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 To view the rest of the report, contact a Caris 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
© Copyright 2024