Therapeutic Strategies in Advanced Ovarian Cancer - Episode 8

Using Novel Therapies in Advanced Ovarian Cancer


Bradley J. Monk, MD, FACS, FACOG: We’ve kind of identified bevacizumab, PARP inhibitors, and immunotherapy as 3 potential targeted therapies. There’s obviously a plan to integrate them into frontline therapy, but it’s going to take a lot of research. I think the only trial that’s on is ATHENA. ATHENA is a 1000-patient frontline trial that compares rucaparib/nivolumab with rucaparib alone. There are 400 patients in each arm, just as maintenance. And then there are 100 patients on nivolumab and 100 patients on placebo to sort out the relative contribution. So, that’s the first one. I think we all understand that there’s an avelumab/talazoparib strategy. Is DUO-O in the public domain?

Kathleen Moore, MD: Not yet.

Bradley J. Monk, MD, FACS, FACOG: There’s a trial called DUO-O that is olaparib/durvalumab. The Merck trial—pembrolizumab/olaparib. Am I missing one? What about niraparib, and they have a TSR-042 checkpoint inhibitor? That’s 5 trials that are somehow putting bevacizumab, a checkpoint inhibitor, and PARP together in the frontline setting. Can we do 5 trials, Katie?

Kathleen Moore, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: Can we do 5 trials?

Thomas Herzog, MD: We can if we’re very mindful of how to use our Cooperative Groups on both sides of the pond.

Oliver Dorigo, MD, PhD: Brad, I might say that it’s going to be important, in the context of all these trials, to look at translational endpoints.

Bradley J. Monk, MD, FACS, FACOG: Thank you for that.

Oliver Dorigo, MD, PhD: We need to learn from tumor biopsies, pre- and post-treatment.

Bradley J. Monk, MD, FACS, FACOG: Biomarkers, right?

Oliver Dorigo, MD, PhD: Biomarkers. We need guidance.

Bradley J. Monk, MD, FACS, FACOG: Leslie, have you heard of financial toxicity?

Leslie M. Randall, MD, MAS: Yes, of course.

Bradley J. Monk, MD, FACS, FACOG: I have 3 targeted therapies, or maybe even 2. Two are only $20,000 a cycle. Come on.

Thomas Herzog, MD: Extra—over what we’re currently paying.

Bradley J. Monk, MD, FACS, FACOG: Yes, right. Where’s the value here?

Leslie M. Randall, MD, MAS: It will depend on the magnitude of benefit. It will depend on if we can use a biomarker strategy to select. If I can offer a patient a therapy that’s going to have significant efficacy, it’s very difficult for me not to offer that based on cost alone. The cost can’t get out of control. Clearly, at some point, the addition of all these agents won’t be sustainable. At some point, we have to come up with some strategy to contain the cost. However, for now, it’s magnitude of benefit and biomarker driven. But interestingly, and we may get to this later, we thought that a PARP biomarker strategy would help us decide who PARPs would benefit the most. But they saw benefit outside the biomarker-positive subgroups.

Bradley J. Monk, MD, FACS, FACOG: I think the argument is, if we’re going to begin to pile on these expensive targeted therapies, we’re going to need more cures. And that’s possible, right?

Thomas Herzog, MD: The Holy Grail of all this is, can we really cure more women with ovarian cancer? Our best opportunity to do so is by treating them upfront with the right drugs and the right combinations. If, indeed, adding an immunotherapy, a PARP, and an anti-angiogenic agent does that, then it’s going to be well worth it. We’ll figure out how to pay for it because it will be well worth it. However, if we just push out progression-free survival a little bit further, and it’s extremely expensive, if we could get the same benefit by using them sequentially, I don’t think it’s going to fly.

Bradley J. Monk, MD, FACS, FACOG: All of us are very passionate about clinical trials. What I hear all the time is, “Oh, you know, there are not enough trials for me to open at my site.” Five trials. International collaboration. I am prepared to make the bold statement that every patient should try to go on a clinical trial, integrating these targeted therapies, which by the way are paid for by the sponsor, hoping that they could participate in a trial that might cure more women. Would you agree?

Oliver Dorigo, MD, PhD: Brad, I agree with you. I think we have to follow and establish a model like the model that the pediatricians have shown us, where the majority of pediatric oncology patients enroll in clinical trials. You can do it through international collaboration.

Bradley J. Monk, MD, FACS, FACOG: Thank you for that.

Leslie M. Randall, MD, MAS: It’s very difficult to treat a patient with carboplatin and Taxol knowing that you have access to these options.

Bradley J. Monk, MD, FACS, FACOG: Right.

Transcript Edited for Clarity