Ovarian Cancer: Maintenance Following Frontline Bevacizumab

Bradley J. Monk, MD: Sharyn, let’s assume you use bevacizumab [Avastin] as the label says. If you have a wild type patient and they respond, then you give the PAOLA [PAOLA-1 (NCT02477644)] regimen or bevacizumab alone. Then it goes back to the same F subnote that says HRD [homologous recombination deficiency] might be helpful. I think you like that. Do you agree with that? Do you like that?

Sharyn N. Lewin, MD: Tom summed it up very nicely. There are definitely different decision points in ovarian cancer. One decision does dictate the other. Whether to use Avastin is irrespective of biomarkers in some people’s mind. But I do believe in the biomarker. It’s not a perfect test. It would be nice to actually see the score if you are using myChoice HRD. But I do think those data influence my personal recommendations for maintenance, once I have that information.

Bradley J. Monk, MD: Thank you for that. If you have bevacizumab started and you have a BRCA mutation, then interestingly, Katie Moore, the category 1 recommendation is not to stop the bevacizumab. Category 1 is bevacizumab plus olaparib. What do you think? If you have bevacizumab going and you have a PR [partial response] or CR [complete response], should stopping the bevacizumab be considered, or should you just add olaparib onto, it which is what the NCCN [National Comprehensive Cancer Network] recommends?

Kathleen N. Moore, MD: That’s another fantastic question we don’t have clinical trial data for. But that was one of the big problems with the olaparib indication in the first place, because SOLO-1 (NCT01844986) did not allow bevacizumab. This was a big problem in many parts of Europe when we ran the study, where it is the standard of care in frontline. People would finish their six cycles with bevacizumab and then stop the bevacizumab so they could go on to olaparib. Does that really make sense? This allows you to use both. Quite frankly, I like it. At the SGO [Society of Gynecologic Oncology] meeting, as you know, Dr Ignace Vergote presented a purely hypothesis-generating—so I’m not at all falling all the sword that this is the thing—modeled comparison of PAOLA-1 and SOLO-1.

The propensity-weighted analysis pulled the patients with BRCA-associated cancers out of PAOLA-1, and then matched them on key prognostic endpoints. They did a weighting so that the patients looked similar in two groups. Then they did this series of comparisons. They did a comparison of olaparib versus olaparib plus bevacizumab. What’s the benefit of the bevacizumab? The hazard ratio was 0.71. There did, by this mathematical experiment, appear to be at least an additive—and probably only an additive—benefit to both. But that’s OK. It was a little bit better. It would be nice to prove this in a real prospective clinical trial, but I doubt we ever do that. The hazard ratio is 0.71.

To some earlier points that people brought up, only in patients with BRCA mutations, they compared olaparib to bevacizumab. The hazard ratio in favor of olaparib was 0.48. There’s still a group of people who think bevacizumab and olaparib are similar, but they’re not in a BRCA-associated cancer. Then they compared bevacizumab versus placebo in these two populations because there’s a group of people who believe that these patients are cured and don’t need any maintenance therapy. The hazard ratio was 0.65 in favor of the bevacizumab. They did a whole bunch of these analyses, but the most interesting of them is this olaparib/bevacizumab versus olaparib that would suggest an additive benefit. You’re certainly not harming people, I don’t believe. You definitely have to watch the safety profile because you’re adding another active agent with toxicities. But if you’re going to start bevacizumab, honestly, I would keep it going and add the olaparib in that population.

Bradley J. Monk, MD: Thank you for that. Tom Herzog, interestingly, in the NCCN guidelines, if you start bevacizumab and a patient has a BRCA mutation, they give you the opportunity to add niraparib to bevacizumab. Obviously, that would not be prospectively tested in an informative way. But there was a study that looked at that here at the SGO. I think that it’s called OVARIO (NCT03326193). Is that right Tom?

Thomas J. Herzog, MD: Yes, the OVARIO trial. Let me present the OVARIO trial, and then I wanted to ask Katie a question. Let me ask you now, since we’re talking. What are you going to do for your next patient, germline or somatic-mutated, whom you would normally follow SOLO-1 for? Would you add bevacizumab?

Kathleen N. Moore, MD: To our earlier point, the decision for bevacizumab is made much earlier, often before I know the germline status of the patient. I’ve made the decision to choose bevacizumab because they have a lot of ascites or bulky disease. That would be my practice, and I’m trying to get a faster, deeper response because I’m trying to get them out of trouble. I get the germline information and in the past, I would have to stop the bevacizumab at the end of chemotherapy, which we all know from a PFS [progression-free survival] standpoint is not how the drug is supposed to benefit. Certainly, I got the response benefit, so now I would leave them on bevacizumab.

Thomas J. Herzog, MD: The answer is yes. If you had previously put them on bevacizumab, you would leave them on.

Kathleen N. Moore, MD: I’d keep it going.

Thomas J. Herzog, MD: Got it. Great. Let me just cover the OVARIO trial, because this is really interesting in terms of the NCCN basically saying that you can substitute these. We do have some data on niraparib with bevacizumab in advanced ovarian cancer looking at Stage III/IV. Remember, there are data that were presented by Dr Melissa Hardesty. It’s a straight phase 2 trial with 105 patients. The primary endpoint is a landmark analysis of how many are progression-free at 18 months. We have the preliminary data from six months, which was really impressive: about 90% of patients were progression-free. The 12-month data came out and the actual presentation is 75% progression-free. A little bit higher in those who had HRD, 88%, versus those who were HR proficient, where it goes down to 66%. The discontinuation rate was 25%, which is not a lot different than what we saw in PAOLA-1, which was about 20%.

Transcript edited for clarity.