RTP On Demand: Current and Future Role of PARP Inhibitors in the Management of Ovarian Cancer (Video Program) - Video 17Perspective on approved and investigational PARP inhibitors
5:08 minutes.
TRANSCRIPTION:
DR LOVE: Let’s talk about the different PARP inhibitors, and particularly in terms of tolerability and whatever you can tease out in terms of efficacy. And you mentioned veliparib, but also at that same meeting, at the ESMO meeting, there was a big presentation on a drug called rucaparib, which we’ve heard a little bit about. It was from, I guess, some data from a couple of studies. What was presented there? What do we know about rucaparib/veliparib, efficacy-wise, first of all? DR MATULONIS: They all have single-agent activity. And so — DR LOVE: In BRCA germline only or non-BRCA, too? DR MATULONIS: Well, so the NRG/GOG did a trial looking at single-agent veliparib in germline BRCA cancer showing a response rate. Response rate was perhaps a little bit lower than a drug like olaparib, but certainly has response, so I think is a real PARP inhibitor. Rucaparib’s data has been presented in a number of different settings, a number of different meetings. DR LOVE: The other person on this program, Tom Herzog, told me that he thought there were going to be 3 approved PARP inhibitors in the near future. DR MATULONIS: Yes. DR LOVE: Including rucaparib, niraparib as well as olaparib. Do you agree? DR MATULONIS: I would agree with that, yes. DR LOVE: Any others that you think might be close to approval? DR MATULONIS: Well, veliparib, no, because its strategy has been to add to chemotherapy in a newly diagnosed patient, and that’s — we don’t have any results on that. The other, talazoparib, has been passed on to a number of different companies, and so they are a little bit late to the ovarian cancer clinical trial queue. So I don’t see that being an approved drug in ovary now. DR LOVE: So trying to, from a macro point of view, compare what we know about tolerability issues, you mentioned the issue of myelosuppression. DR MATULONIS: I think as a class effect PARP inhibitors have 2 main toxicities. One is gastrointestinal, and then secondly bone marrow suppression. So I think you have to expect both when you start any of these PARP inhibitors in patients. But you’re correct, so you have to watch out for thrombocytopenia, watch out for neutropenia and watch out for anemia. DR LOVE: And again, looking at, at least these 3, any gut — interestingly — gut feeling about the relative GI toxicity? Do you think it’s the same? Do you think some are worse? DR MATULONIS: I think the GI toxicity is pretty much the same. And I’ve been impressed how some patients are just more sensitive to the GI toxicity. I guess what we don’t have yet — and that decision-making is not there yet — if you’ve got 3 or even 2 PARP inhibitors in play, and you start off with one and you say, “Wow! You’re having a lot of nausea from this drug. Let’s see if we switch you to another one, what will happen,” much like aromatase inhibitors in breast cancer if somebody was having significant joint pain or headaches or whatever, if you switch them to another aromatase inhibitor, did that make a difference? Well, I think the problem is that these are class effects. And there’s absolutely no data on moving from one PARP inhibitor to another. DR LOVE: Yes. I think the aromatase story is almost like lore more than science. DR MATULONIS: Exactly, that’s right. DR LOVE: Docs say, “We just try it. We don’t know why sometimes.” DR MATULONIS: Yes. DR LOVE: But what about efficacy? Do we know right now, for example, if somebody has disease progression on one PARP inhibitor, whether or not they might respond to another? DR MATULONIS: I think that’s more of a case of the cancer continuing to be sensitive to a — potentially sensitive to a PARP inhibitor, much like reuse of platinum. And certainly in my practice, if I’ve had a patient who’s been on — and I can only really say this with olaparib, because we have this capability of reusing olaparib again. But if a patient had done very well on a clinical trial, maybe came off because of progression but it’s not really clinically significant, but she has to come off the trial, I’ve, in few certain circumstances, reused olaparib, and in some circumstances showing responsiveness. But again, that’s not surprising because of the platinum story, where you can use platinum, patient progresses, then you come back with another platinum at another time point, again showing this continued sensitivity to the drug. But what I can’t say is that, if you switched PARP inhibitors, would you get better efficacy? I mean, they’re PARP inhibitors, so I think they work in similar ways. So to me, they should all work. |