DR MATULONIS: I think another issue that comes up is — and I don’t know how this is going to go. But as we’re thinking about germline testing versus somatic testing and if we take a cancer, and that cancer initial — I mean, there’s a few issues here. One is that the patient’s diagnosed and we submit that cancer to some sort of next-gen sequencing. And you find underlying deleterious BRCA mutation. And then that patient would then go on to germline testing to see whether or not she’s got a germline mutation or this is purely somatic. And it depends upon how the kind of tumor genomics field goes. I mean, right now, we’re not doing that. We’re starting with germline testing.

And then the other whole piece, of course, is around the HRD assays and how predictive or not predictive they are, and where they fit in. And I think, obviously, the regulatory agencies are going to take a look at this data both here and in Europe and make that determination. But the one issue with HRD assays is that you’re taking that result and you’re taking it — and you’re getting that result from an initial tumor, so from a cancer at initial diagnosis, where we know that 80%-plus patients, their cancer at that point is going to be sensitive to chemotherapy, sensitive to platinum-based chemotherapy.

And then, as patients go into remission and then recur, and then recur again, that cancer sensitivity to platinum changes, and it becomes increasingly platinum, and it can also become increasingly PARP inhibitor resistant. So those HRD assays really look at a moment in time, and a moment in time when the cancer is in pretty good shape in terms of being able to respond to a platinum-based chemotherapy.

So I think that there’s a whole field now that’s emerging with DNA repair experts at the forefront of this in terms of, at that moment in time for a patient, what’s her cancer doing? Is it going to be responsive to a PARP inhibitor? Do we have to use a PARP inhibitor combination? What happens if the patient’s on a PARP inhibitor and progresses? I mean, these are all open questions right now.

Treatment strategies in the management of ovarian cancer (OC)

Mechanism of action of PARP inhibitors and importance of BRCA testing

PARP inhibitors as primary treatment after multiple lines of therapy

PARP inhibitors as maintenance therapy

Tolerability of olaparib

Treatment options after olaparib failure

Differences among PARP inhibitors

Future directions in OC research