RTP On Demand: Current and Future Role of PARP Inhibitors in the Management of Ovarian Cancer (Video Program) - Video 20Potency and side-effect comparison of PARP inhibitors
1:58 minutes.
TRANSCRIPTION:
DR LOVE: At this point we have a lot less data than, let’s say, aromatase inhibitors in breast cancer or checkpoint inhibitors in a bunch of cancers, where people kind of feel like they’re equivalent. From your point of view, do you think it’s going to shake out that, for example, these 3 drugs that maybe end up all approved at the same time, for example, from a tolerability point of view at this point, can you separate them out? DR BIRRER: It’s pretty tough. I think a lot of us get — at a 50,000-foot level would say these are roughly similar molecules. There are some subtle — DR LOVE: Although it did seem — DR BIRRER: There’re some subtle differences. Rucaparib, it looks to me like the anemia is a little higher than the other two. And for niraparib, thrombocytopenia is definitely higher than the other two. But it’s pretty subtle. And they’re mostly — those toxicities are manageable. The only other difference I know is olaparib had used a capsule formulation, which was really horrible. It was 8 to 16 capsules a day. Patients really had a problem with it. They’re now on to a tablet form, which will be easier. But that’s about it. The only PARP inhibitors that extend — that look like they’re different — is one on each end. Veliparib looks, on a biochemical level, to be in order of magnitude a weaker binder than the 3 we’ve been talking about. Whether that binding correlates with response, we don’t quite know. But it is interesting. Veliparib has been combined with chemo, and it looks like it’s easier to combine it with chemo than the other drugs. The other one that’s out in early drug development. But that drug is interesting that it has a thousandfold higher binding capacity than all of these drugs. And so, of course, you immediately ask the question, is that a good thing or a bad thing? Does that mean it’s going to be that much more potent against the tumors, or are we going to see a lot more bone marrow toxicity? I don’t know the answer. It’s just the — it’s going through Phase I now, entering the Phase II. |