OvAware Program Highlights: Ovarian Cancer Risk Blood Test (Phenomenome Discoveries Inc., March 2016)

Date: February 29, 2016
Source: Phenomenome Discoveries Inc., 204-407 Downey Road, Saskatoon, Saskatchewan.
Author: Phenomenome Discoveries Inc.
Type: Report

A product overview prepared by Phenomenome Discoveries Inc. in March 2016 describing OvAware, a blood test measuring ratios among eight lipids in the blood as a risk factor for ovarian cancer. At the time of writing, OvAware was pending approval by Health Canada and other regulatory bodies, and was run as a research-use-only laboratory-developed test at Phenomenome Laboratory Services Inc. The document describes validation studies including a Japanese cohort of 122 ovarian cancer patients and 96 controls, and a Canadian validation involving 234 ovarian cancers, 62 endometrial cancers, and over 600 control female samples.

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Program Highlights Page

Product Description

OvAware™ is a blood test that measures the levels of several lipids in the blood as a risk factor for ovarian cancer. The output is a quantitative value to determine whether a woman has increased or decreased risk of ovarian cancer.

Clinical Utility

The purpose of OvAware is to reduce ovarian cancer associated mortality by identifying a subset of women from the general population who have increased risk, and who should consider further screening options or possibly opportunistic salpingectomy (surgical removal of the fallopian tubes). Screening based on CA-125 and transvaginal ultrasound alone has failed to yield survival benefits, with up to 70% of cases still diagnosed at a late stage. Since it is now believed that many ovarian cancers originate in the fallopian tube, attention has recently shifted to the use of salpingectomy as a prophylactic means of reducing risk among women. Performing the procedure, however, on all women is likely not feasible. OvAware, therefore, represents a necessary tool with respect to this approach by identifying high-risk subjects who should consider prophylactic options, while eliminating the need for low-risk women to undergo the procedure.

Clinical Studies

OvAware has been evaluated in numerous clinical studies including:

Discovery sample population where several ultra long chain polyunsaturated fatty acids and ethanolamine phospholipids showed altered profiles in ovarian cancer patients (n=20) versus controls (n=50).
Reductions in lipid panels discovered above were validated in samples from Japan (122 ovarian, 96 control), and the dataset used to refine the number of analytes based on logistic regression and linear discriminant analysis. The resulting receiver-operator area under the curve (ROC-AUC) was 0.99 in differentiating ovarian from control.
Canadian validation 1: This was a large study of ovarian cancers (n=234), endometrial cancers (62) and other benign/borderline cases (202) combined with over 600 control female samples from two independent geographic regions. Results were consistent with an ROC-AUC > 0.95 for control versus ovarian cancer.
Canadian validation 2: In this study, which is currently in progress, 917 samples are being analyzed in a blinded manner. The samples represent over 200 individual cases with longitudinal collections during treatment, as well as a subset of women who are BRCA1/2 carriers.

Biological Mechanism

OvAware measures the ratios among eight lipids in the blood. Two of the lipids are 28-carbon long-chain unsaturated fatty acids involved in controlling inflammation within the body, while the other six lipids are glycerophospholipids containing ethanolamine and combinations of 18:1, 18:2, 18:3, 20:4 and 22:6 unsaturated fatty acids. The ratios between the lipids suggest an overall increased fatty acid desaturase activity, or increased de novo fatty acid synthesis in ovarian cancer patients, both of which are well known to contribute to a cancer phenotype.

Test Method

The OvAware test is performed on 15µL of serum, collected using conventional phlebotomy. The assay is based on tandem mass spectrometry, and has been optimized to run on PDI’s custom platform that can process up to 1000 samples per day. A proof-of-concept blood-spot version of OvAware has recently been developed to eliminate the need for conventional phlebotomy and improve distribution. The prototype product is based on a helical serum-separator technology that requires approximately two drops of blood from a finger-prick.

Regulatory Status