Case study 1 Flashcards
What are 3 ways biomarkers fail to reach the clinic?
Fraud
True discovery leading to weak clinical performance
False discovery leading to original claims failing validation
What was the ovarian cancer trail that failed?
Early Detection Research Network
Dr Gil Mor
What did Dr Gil Mor’s trail looked at
6-protein panel detected ovarian cancer in only 34% of women diagnosed with disease within a year
What was Dr Gil Mor’s downfall?
Inappropriate statistical calculation & unproven claims for the test
Did Ovasure reach marker?
Yes for 4 months but FDA intervened
What was Genomic Health’s aim?
Development & commercialization of genomic-based clinical diagnostic tests for cancer to allow for individualised treatment decisions
What were 5 subtypes of Genomic health’s mRNA gene-expression profiling studies breast cancer testing?
Luminal A - most favourable
ERBB2 (HER2) - poor
Basal like (triple negative) - poor
Luminal B
Normal breast-like
When was genomic health founded?
2000 following first major study in 1994
When was Genomics Healtth Proof of concept completed?
2001 - demonstrated gene expression profiles from FFPE tumours
What were 5 reference genes in Genomic Health?
beta actin
GAPDH
RPLO
GUS
TFRC
What was genomic health’s assay used for?
Assess likelihood of recurrence using archived tumour samples from 668 patients with N-tamoxifen treated Bca
What were the 3 recurrence scores?
Low risk <18
Intermediate risk 18-25
High risk > 25
When was the Oncotype Dx BC test launched?
2004
What did the SWOG 8814 study evaluate?
Post-menopausal patients with N+, ER+ BCa treated with chemohormonal tx vs tamoxifen alone
What did SWOG 8814 study find?
Chemotx of no benefit in women with low RS despite N+ -> added CHT in intermediate scores of limited value
High RS - large benefit from chemotherapy
What cancers are genomic Health Dx test used for?
Breast
Colon
Ductal carcinoma in situ
Prostrate
When did SEER registry recognise the Genomic Health Dx test was effective?
2015
When did TailorX support the Oncotype Dx for BCa?
2015
When did the UK recommend Oncotype Dx test by NICE guidelines?
2015/2016
When can chemotherapy be spared in?
70% of BCa Pts with LN-, ER+, HER-2-
What did the OncoMasTR Molecular Score look at?
3 gene mRNA panel looking at OXM1, PTTG1 and ZNF367
What does OMclin1 combine?
OMm, tumour size, grade & nodal status
What does OMclin2 incorportae?
OMm, tumour size & nodal status
What were Omm, OMclin1/2 in TransATAC highly prognostic for?
early & late DR in 646 women with post-menopausal early-stage ER+ BCa receiving 5 yrs endocrine therapy
