Those are measures that are part of the Myriad test that is now being prospectively tested in the NOVA trial (NCT01847274), which is looking at the PARP inhibitor niraparib versus placebo in patients with platinum-sensitive recurrent ovarian cancer on the heels of receipt of platinum-based chemotherapy.
The purpose of expanding the identification of tumors responsive to BRCA
is that approximately 20% to 25% of ovarian cancers either have somatic or a germline BRCA
mutations. We know that, overall, about 50% of high-grade serious cancers are what we call HR-deficient or have these homologous recombination deficiency properties that would allow it to be sensitive to carboplatin or PARP inhibitors.
The purpose of these other homologous recombination deficiencies tests are to try to capture those patients who will not necessarily have a BRCA
mutation, but are also going to be sensitive to carboplatin or a PARP inhibitor.
The purpose of doing these tests is to look at the tumors and see if there has been evidence of DNA-repair problems. There are these genomic scars, where breaks happen in the DNA. However, they don't always get fixed correctly, so there's a scar.
The more scars you have, the more evidence you have that those tumors may be more receptive to a drug such as a PARP inhibitor.
How would that information impact research and practice?
With that kind of information, it would allow one to predict the responsiveness of a cancer to a PARP inhibitor, but it also allows that test to be embedded within a clinical trial. This way, you can prospectively not only test the drug, but also use an appropriate biomarker to tell you which patients would be appropriate for this drug or not.
1. Liu J, Barry WT, Birrer MJ, et al. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. J Clin Oncol. 2014;32: 5s. (suppl; abstr LBA5500).
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