Advanced Ovarian Cancer: Emerging Therapies

Transcript:

Bradley J. Monk, MD, FACS, FACOG: If you look at what’s coming up, I think we said that GOG-0218 may lead to FDA approval. The next thing that’s probably going to happen in frontline advanced ovarian cancer is that we’re going to hear about a study called SOLO-1. Tell us what SOLO-1 is, and tell us how that might impact practice, depending on what the results are, Katie?

Kathleen Moore, MD: SOLO-1 is a randomized phase III study of olaparib maintenance therapy following frontline chemotherapy in patients who had a partial or complete response to therapy, who also have a germline BRCA mutation. The primary endpoint is progression-free survival, and it will be presented soon.

Bradley J. Monk, MD, FACS, FACOG: If SOLO-1 is a positive trial, Leslie, are you going to say, “Oh, no, now I can’t decide—bevacizumab versus olaparib,” at least in the BRCA-mutated patient. How are you going to figure that out?

Leslie M. Randall, MD, MAS: I think the germline BRCA mutation status will drive that decision in the frontline setting.

Bradley J. Monk, MD, FACS, FACOG: OK. Some people have said, “Well, it has to be better than platinum-sensitive maintenance as second-line therapy.” There was SOLO-2. If looks about the same as SOLO-2, maybe I’m not going to use it in the frontline setting. I’ll just use it as a second-line option. Is that the way you’re going to look at it, Tom?

Thomas Herzog, MD: I have to look at the data, but that doesn’t carry a lot of weight for me.

Leslie M. Randall, MD, MAS: If I were going to ration PARP in the germ line population, I might save it for single-agent treatment later and may not decide at what point I’m going to give it as maintenance.

Bradley J. Monk, MD, FACS, FACOG: Oliver?

Oliver Dorigo, MD, PhD: I would be one of the people who would suggest that the progression-free survival, the benefit after first-line treatment, would be greater than after the current treatment of ovarian cancer and PARP. Because biologically, if you have lesser cycles of platinum chemotherapy, we do know that platinum can reverse BRCA mutations. Although that is not a very frequent event, we have to take this into account.

Bradley J. Monk, MD, FACS, FACOG: What’s going to happen is that because SOLO-1 is an event-driven analysis, the medians will not be met. You won’t be able to look at the medians. And so there will be a hazard ratio. It’s hard to get much better than the hazard ratio of SOLO-2. The hazard ratios will look the same. And then we’ll have something to fight about again.

Thomas Herzog, MD: More to talk about.

Oliver Dorigo, MD, PhD: SOLO-1 just lowered the number of events needed for the interim analysis.

Bradley J. Monk, MD, FACS, FACOG: I understand. So GOG-0218 will likely lead to FDA approval. SOLO-1 is going to read out. The next thing that’s going to happen is a study, PAOLA-1, which will probably happen very soon. PAOLA-1 is a randomized trial that now adds it together. It takes maintenance bevacizumab and then puts olaparib in that maintenance phase. Do you have any idea when that is going to be available?

Kathleen Moore, MD: I think in 2019.

Bradley J. Monk, MD, FACS, FACOG: So we don’t know. So GOG-0218 will likely get approved. SOLO-1 will report. PAOLA-1 is olaparib/bevacizumab. The next thing will probably be JAVELIN OVARIAN 100, which is the addition of a checkpoint inhibitor to frontline chemotherapy. Is that something you’re excited about, or do you think that the chance that checkpoint inhibition will be integrated into frontline therapy is probably not a good idea?

Oliver Dorigo, MD, PhD: We are excited about immune checkpoint inhibition and immunotherapy in general, Brad. It remains to be seen whether this treatment is tolerated. We have avelumab going into the first-line setting. We’re looking at atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin in GOG-3015. It remains to be seen whether a stimulation of T cell responses in the first-line setting really makes a big difference. It’s difficult to predict.

Bradley J. Monk, MD, FACS, FACOG: We all have to admit that the idea of adding a checkpoint inhibitor to chemotherapy might cause immunogenic cell death. We’ve seen that in lung cancer, and we’ve seen it in other settings. So, stay tuned.

So, we have GOG-0218, SOLO-1, PAOLA-1, and JAVELIN OVARIAN 100. The fifth thing that will probably happen within the 18-month to 2-year time frame is that PRIMA will finish. Tell us what PRIMA is.

Leslie M. Randall, MD, MAS: This is looking at niraparib maintenance in the frontline. It looks at all-comers in the HRD subset. My germline BRCA argument is going to be out the window. Now I have to decide if I will use PARP therapy in my all-comers.

Bradley J. Monk, MD, FACS, FACOG: Isn’t that great? We’ve got 5 trials. Well, GOG-0218 is not labeled yet, but we have 4 other trials, frontline, that have all enrolled, that will report within the next year to year and a half.

Kathleen Moore, MD: We also have VELIA.

Bradley J. Monk, MD, FACS, FACOG: Tell me about VELIA.

Kathleen Moore, MD: VELIA was GOG3005. It was standard chemotherapy with or without veliparib, and then in veliparib maintenance versus placebo.

Bradley J. Monk, MD, FACS, FACOG: That would be the fourth PARP inhibitor to be approved. Wouldn’t that be great?

Kathleen Moore, MD: We should hear results on that next year as well.

Transcript Edited for Clarity