Practical Implications for Treatment Strategies in Advanced Ovarian Cancer - Episode 5

Need for Frontline Comparison Trials in Ovarian Cancer

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Bradley Monk, MD, FACOG, FACS: Michael, the point is that, when we had recurrent maintenance, all 3 indications were the same. We didn't have to have this conversation. We could talk about nuances, and niraparib is once daily. For olaparib today, there are 7 indications and 4 tumor types for olaparib. That’s cool, right? Prostate, pancreatic, breast, and ovarian cancers. It’s not that way anymore. Now the indications are different. Are they different because of the way the clinical trials were designed, or are they different because the agents are different?

Michael J. Birrer, MD, PhD: It’s a great question. Getting back to the PAOLA-1 comparison, the Europeans, particularly Eric Pujade-Lauraine [MD, PhD,] made a big deal of the bevacizumab comparative arm neutralizing that effect in HRP [homologous recombination proficient]. I don’t buy that. It should at least be additive. In addition, if you look at GOG-0218, if you remember what happens when you stop the bevacizumab, the curves come back together.

Bradley Monk, MD, FACOG, FACS: It’s a banana curve, right.

Michael J. Birrer, MD, PhD: Yes, and that’s inherent. It’s in PAOLA-1. It raises the issue that there’s something’s fundamentally different between the PARP inhibitors. They are probably the best data we have to suggest there’s something there. I’m the eternal skeptic, so I don’t buy it yet, but it’s worth some thought. Maybe we should design a direct comparison trial.

Bradley Monk, MD, FACOG, FACS: To your point, that’s what the NCI [National Cancer Institute] is supposed to do, right?

Michael J. Birrer, MD, PhD: Yes.

Bradley Monk, MD, FACOG, FACS: You know the pharmaceutical industry isn’t going to do that. That’s ideally what the cooperative group should do, and I completely agree with that. And the NCI should look at sequencing. Giving PAOLA-1, it would just be chemotherapy, but if you give PRIMA, it should be bevacizumab as a second-line therapy.

Michael J. Birrer, MD, PhD: Another way to address it is, after progression on olaparib, do patients respond to niraparib?

Bradley Monk, MD, FACOG, FACS: Right. Leslie, I’m going to follow this and then I’m going to move on. I don’t mean to belabor the point….

Leslie Randall, MD, FACOG: On this point, I want to say something.

Bradley Monk, MD, FACOG, FACS: I’m going to give you a point right now. Why don’t you say something, then I’ll ask you a question? Go ahead.

Leslie Randall, MD, FACOG: I want to chime in on this discussion; it’s important. Shannon is spot on. This is a lot of trial design: it’s population, and it’s control arm. It’s PRIMA, no bevacizumab. It’s PAOLA, different PARP inhibitor. In the HRP group in PAOLA, it looks like bevacizumab alone may be enough for them, and they may just not benefit from PARP inhibition.

If you look at PRIMA, they did benefit, but we’re talking about all these subpopulations. These are underpowered, hypothesis-generating assessments. In the normal situation, we would use this to design the next trial, right? The fact that the PAOLA label is based on that subset is surprising to me for that reason, but I guess it’s because it was so negative.

Transcript edited for clairty.