The Role of PARP Inhibitors in Ovarian Cancer - Episode 16

Treating Recurrent Patients

A consideration of whether the AVANOVA phase 2 mono- or combination therapy is preferable, and a discussion on the future of ovarian cancer management.

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Maurie Markman, MD: We have data that show, in the recurrent setting, that you can combine a PARP [poly ADP ribose polymerase inhibitor] with bevacizumab. Has that become a potential standard of care where you can now do that and not have to worry about whether you give bevacizumab or a PARP? What about just giving bevacizumab and PARP together?

Wendel Naumann, MD: I’ve certainly done it, again off-label. But, yes, if somebody is started on BEV [bevacizumab] and has a really good response, and I think that they would be a good candidate for PARP inhibition, I would add a PARP to it or at least discuss that. But again, we don’t know what the benefit over bevacizumab is alone, and now you’re adding toxicity and expense to the regimen. So I don’t know, Mike?

Michael Birrer, MD, PhD: I agree completely. AVANOVA showed, I think, that it’s relatively safe. I don’t think it’s very toxic. And the only issue is the issue you’re bringing up, Wendel, which is there’s been this hand-waving, an issue about, well, when you make a tumor hypoxic, you produce a pseudo-HRD [homologous recombination deficiency] so the PARP inhibitors can be more effective. Frankly, what I’ve seen is more additive than synergistic. But that wouldn’t argue necessarily against using the combination because they’re both effective.

Wendel Naumann, MD: That’s an excellent question. It would be great if we had a scientific answer to whether there is true synergy between these agents, and that’s really what you’re getting at.

Michael Birrer, MD, PhD: Yes, and the other combination that’s hot, in my mind, is cediranib and olaparib. Those are now in 2 large randomized phase 3 trials.

Wendel Naumann, MD: But again, is the activity synergistic or additive? And that’s the other issue.

Michael Birrer, MD, PhD: Yes. And frankly, TKIs [tyrosine kinase inhibitors] aren’t real easy in ovary patients. They’re doable but they’re tough.

Maurie Markman, MD: This has been extremely informative. Before we end this discussion, I’d like to get final thoughts from each of our panelists. Mike?

Michael Birrer, MD, PhD: Well, I think it’s just incredibly exciting times, the most exciting time for me in my years in oncology with all these multiple approvals and now these combinations, things that we’ve talked about. And what that translates into is a terrific advantage for our patients.

Maurie Markman, MD: Agreed. Annette.

Annette Hood, PharmD, BCACP: I think now that we have all these new oral chemotherapy options, it really does increase the role of the pharmacist with patient counseling, so we can talk about monitoring adverse effects, managing adverse effects, and managing compliance as well, and helping with cost.

Maurie Markman, MD: Wendel?

Wendel Naumann, MD: A lot of this is deciding how we’re going to practice. When we see our newly diagnosed patients with ovarian cancer, what are we going to tell them? How are we going to sequence the genetic testing? What genetic tests are we going to get? How are we going to use that information? What regimen we’re going to pick. Now, when they recur, we have to decide what regimen we’re going to use but, all of the recurrent studies were done before we had the upfront treatment. So they’re sort of nullified, and we’re going into the unknown. I think that’s probably, as I look at this, changing so fast, it’s very difficult to keep up with. I’d be interested to see the upcoming trials in the frontline setting to see how things are changing again. We could have prolonged bevacizumab now with the BOOST trial. We could have the addition of I/O [immune-oncology] upfront. We just don’t know.

Michael Birrer, MD, PhD: It’s why these panel discussions are so important because we go over these issues.

Maurie Markman, MD: Yes. Obviously, the trials answer a question, and then we have to interpret them. I think that’s what this is all about.

Wendel Naumann, MD: There are always 5 or 10 questions generated from every answer that we get.

Maurie Markman, MD: And if that is not the case, there’s a problem. Well, I want to thank you all for your contributions to this discussion. And on behalf of our panel, we thank you for joining us, and we hope you found this discussion to be useful and informative.