DR LOVE: Fifty-four-year-old woman with a germline BRCA2 mutation is on olaparib and doing well, responding. Ten months into therapy, the patient starts to show slow, asymptomatic growth of peritoneal metastatic nodules. Doesn’t say anything about the CA-125, but let’s assume it’s going up. The question is, would you keep the olaparib going and add something else, like chemo or bev, like the trastuzumab thing or the androgen suppression in prostate cancer?

I’m guessing it hasn’t been studied, but —

DR MATULONIS: Hasn’t been studied, right.

DR LOVE: Does it make sense?

DR MATULONIS: Yes. And this happens a lot, because I do think — and, again, I don’t have any great data on this, but certainly from my own practice, I think PARP inhibitors will suppress the growth of tumors. So you can have this low level of progression, but the patient feels great. Maybe her CA-125 is starting to go up and she’s showing some evidence of growth, but, to me, it wouldn’t be clinically significant.

So I think the doc has to make that determination. Is this clinically significant or not? And is this a reason to change treatment strategies, because probably the patient is saying, “Doc, I don’t want to come off this drug because I’m actually doing okay on it. I feel all right.” So I would say, if there is nonsignificant clinical growth, like there’s just some millimeter changes in peritoneal implants and her CA-125 is just maybe headed up slightly, I might say, “Let’s recheck you in 2 months. And let’s see how you’re doing.”

But if the doc says, “Okay. This is clinically significant. I’m concerned,” then you’re right. Then we don’t have a clear strategy moving forward. And there are strategies afoot. My colleague Amit Oza has a trial that is adding cediranib to olaparib at olaparib progression. We’re working on a trial with our colleagues at MD Anderson that’s adding a WEE1 inhibitor to a PARP inhibitor at the time of PARP inhibitor progression. So there are now strategies that are being determined that would allow a patient to stay on a PARP inhibitor, but you add something to that. And whether it’s another agent that is involved in DNA repair or totally another one, like an antiangiogenic or maybe even immunotherapy, but we don’t know.

DR LOVE: How about outside a trial setting? This doc, for example, says, “How about if I just add some bev?”

DR MATULONIS: Have I seen that happen? Yes, I have. Do I have any evidence — does anyone have any evidence that’s of benefit? No, you don’t know. You don’t know. I don't know. I mean, I guess you could, but there’s absolutely no data to suggest that that would be a good thing. I think what I would not do is add chemotherapy, because of the overlapping bone marrow toxicities of PARP inhibitors and chemotherapy. There’s really no justification for adding chemotherapy to a PARP inhibitor. That patient will for sure get into problems with myelosuppression.

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