DR HERZOG: There’s some subtle differences that we see between the PARPs, the big 3 that are either on the market or close to market, that being olaparib, rucaparib and niraparib. The thing we see more with the olaparib is the fatigue, a little more GI, I think. We usually premedicate these women with antinausea drugs.

DR LOVE: What do you tell them in terms of food and how to take the pills?

DR HERZOG: Mainly we follow the package insert on how to take the pills. We make sure that they have plenty of antinausea medication available to them.

DR LOVE: Another issue we’ve heard about, at least with olaparib, and you can educate us about the other 2, also, is anemia. To what extent have you seen it? How do you manage the anemia? If the patient’s responding, will you transfuse them, for example?

DR HERZOG: We will. They just feel better, Neil, if you give them a couple of units of blood, if they’re getting down under 8, especially if they’re laboring, having any type of symptoms. I try to transfuse them up a little bit to try to keep them closer to 10.

DR LOVE: Based on your global experience and reading the literature, roughly what fraction of patients do you think have problems with anemia?

DR HERZOG: Actual problems where you have to transfuse, it’s probably well under 10%.

DR LOVE: And I know there were concerns. I don’t know if there’s any data about the potential for second cancers, carcinogenesis. What do we know about that and what’s the basis for this whole issue?

DR HERZOG: The biggest thing is myelodysplastic syndrome and those types of issues. You’re dealing with a pathway that you’re inhibiting DNA repair. So from a hypothetical and theoretical standpoint, you certainly have to be concerned about secondary cancers if these patients are on these drugs for a prolonged period of time. For those patients we’re dealing with — or in the current label in the US — a fourth line and beyond, really their ovarian cancer is going to take precedent.

But, to your point, what about if we move these drugs up in the treatment line as maintenance, say, second-line platinum-sensitive, for example, of which still a small percentage of those would be cured, but some of those patients live quite a long period of time. What we have observed is some higher incidence in some studies of myelodysplastic syndrome.

The problem is that — I’ll give you a good example. We had a patient, I think it was about 6 months ago — we were getting ready to put her on a PARP inhibitor. And lo and behold, literally about 2 weeks before we start, she developed myelodysplastic syndrome. So it’s part of the natural history of ovarian cancer for these women who have been through 4 and 5 different cycles of DNA-damaging drugs. And so it’s certainly hard to separate something that happens at 1% or so at a time and try to figure out whether there’s truly an increase there or not. But it is something I know the FDA and the regulatory authorities are watching closely in these patients.

DR LOVE: Based on, again, the data we have and maybe any clinical experience you have, how would you compare the issue of GI toxicity, anemia, potential carcinogenesis, let’s say, amongst the 3 PARP inhibitors you just mentioned?

DR HERZOG: I think with niraparib we see a little more in the way of platelet issues, maybe a little more anemia. So I think there’s a little bit of an interplay between these. We haven’t really seen the robust data set from rucaparib yet. And that’ll be forthcoming from their large Phase IIIs. So I think it’ll be interesting as all these data emerge in trying to differentiate between these PARP inhibitors.

From a scientific level, we would think that they’re more similar than different in the sense of their mechanism of action, although there are some of those who propose slightly different percentages of PARP-trapping and some secondary mechanisms of action-type platforms. But I’m not sure that those are really operational and they really mean anything in the clinical arena.

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