DR LOVE: Knowing that we were going to chat today, I kind of put out my feelers to people out there in the community and said, “Hey, give me some questions and cases.” And here’s my favorite one: 45-year-old lady, BRCA2 germline mutations, diagnosed with Stage IIIA serous ovarian cancer, undergoes optimal debulking surgery, 6 cycles of adjuvant carbo/paclitaxel. She’s now free of disease, has a normal CA-125, but apparently is a very educated patient and found out about the niraparib maintenance study, and wants to know if the doc will prescribe maintenance olaparib.

DR MATULONIS: Yes.

DR LOVE: What would you say?

DR MATULONIS: Well, based upon the confines of the US FDA —

DR LOVE: Well, let’s say maybe the patient will pay for it. Let’s make it easy.

DR MATULONIS: Yes. So that trial is called SOLO-1. And SOLO-1 is for exactly that patient population, newly diagnosed, has an underlying germline BRCA mutation or somatic BRCA mutation. At the completion of chemotherapy, they’re randomized to either olaparib versus nothing, and no results. So we just heard about SOLO-2, but that’s in maintenance. SOLO-1 is the patient who is at risk, but you don’t know.

And I’ve been asked by patients that before. My answer is no, I would not do it, because, (A) we don’t have data. Secondly, this patient may be cured. I mean, there is a subset of women, as we know — she’s already said she’s Stage IIIA, so she’s already got a better prognosis than somebody with a Stage IIIC. She was optimally cytoreduced. These are all good prognostic features. She’s young. So there’s going to be a percentage that she may be cured, 20%-25%, possibly. Yes?

So why give her a medication that we know has side effects? (A) We don’t have data. Secondly, she may be cured. And then thirdly, there are going to be potential side effects of a PARP inhibitor.

I think it’s also the “do no harm” because you have a patient who may actually do quite well. And I think the other piece is that you don’t know what olaparib is going to do in this situation. Is it going to prolong progression-free survival? Is it going to have an impact on overall survival? Is it going to make her cancer more curable, and with what downsides? The downsides being these risks of potential AML/MDS, although I think very low for her since she’s only had 1 round of chemotherapy, but she’s going to take a pill. She’s going to take not just a pill, she’s going to take 16 capsules per day.

DR LOVE: So, I’ll ask you to put your crystal ball hat on and predict 10 years from now, what you think the impact of PARP inhibitors would be up front in this situation, in patients who never — who’ve just gotten chemo for the first time, platinum-sensitive, platinum-resistant. When it’s all played out and we’ve studied all those arenas, how do you think the impact of PARP inhibitors are going to compare in those 3 scenarios?

DR MATULONIS: Well, I think certainly for patients who have germline BRCA, hopefully by 10 years from now we’ll have identified which patients within that gBRCA group are going to have the best responsiveness, because even within a gBRCA group or a somatic BRCA group, not all patients are going to respond to PARP inhibitors, so really teasing out which patients are going to have the highest response. So for sure, PARP inhibitors will be there.

I think PARP inhibitor combinations are going to be critical and, right now, combining them with the other active biologic agents in ovarian cancer. So number 1 would be antiangiogenics. There are — the PAOLA trial that is looking at the combination of olaparib plus bevacizumab in patients who are newly diagnosed. And so what do you do adding a PARP inhibitor to bevacizumab?

But then also immuno-oncology agents and PD-1/PD-L1, which we know, as single agents, have very limited activity in ovarian cancer. So they also are going to need some kind of a boost, and whether or not that’s combining with a PARP inhibitor or combining with other agents. So I see the landscape further moving along the breast cancer landscape, where you carve out the patient populations into smaller subgroups, those requiring a PARP inhibitor, those requiring a PARP inhibitor combination, or not, and focusing on something else.

I think SOLO-1 is going to tell us how important a PARP inhibitor is going to be for those women who have an underlying germline mutation. Other PARP inhibitors, specifically niraparib, are being tested up front. Veliparib, which we haven’t talked about, is being tested in an up-front NRG trial. So you’ll have a number of studies reporting out in both gBRCA patients, along with non-gBRCA or wild-type patients, and kind of seeing what the results look like. What’s the risk-benefit ratio looking like.

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