Bevacizumab’s Role in Recurrent Ovarian Cancer

Bradley J. Monk, MD: Katie Moore, I saved bevacizumab for you because you did a lot of these PARP inhibitor studies. Is there still a role for bevacizumab in recurrent ovarian cancer? And if so, tell us about that opportunity.

Kathleen N. Moore, MD: I absolutely think there’s still a role for bevacizumab in recurrent disease. We know, from randomized phase 3 data, that bevacizumab is still as effective even if you’ve had prior bevacizumab. Even for patients who recurred during prior bevacizumab, if they are put back on it with chemotherapy and bevacizumab to follow, the benefit remains. So bevacizumab after bevacizumab has been demonstrated. Now, I think the new indications will inform some of the opportunities for bevacizumab, but quite a few more women will be eligible, thankfully, for PARP inhibitor in the front line. You all just nicely reviewed SOLO-2, ARIEL3, and ENGOT-OV16/NOVA, which were all done in PARP-naive women.

Now we are going to have a lot of these patients who are PARP pretreated and may have progressed on a PARP; we don’t have data yet on the efficacy of PARP after PARP. We do have that data for bevacizumab, and a lot of them will not have received bevacizumab in the front line.

The role of bevacizumab actually comes roaring back now in this line of therapy, and the nice thing is that it’s been so well studied. The original study GOG-0218 and OCEANS limited us to carboplatin/paclitaxel and carboplatin/gemcitabine, which are both nice backbones. Now we have data out of the AGO [German Gynecological Oncology Group] with carboplatin and pegylated liposomal doxorubicin, which is my favorite regimen, just because the schedule is so nice for patients, showing that bevacizumab added to that is not only safe but is at least equivalent to carboplatin/gemcitabine plus bevacizumab and maybe a smidgen better.

There are now 3 backbones in a platinum-sensitive population in which you can use bevacizumab. I think the role of bevacizumab in this line of therapy probably went down a little bit with the PARP approval. But now that PARPs have moved to the front line, I think bevacizumab is actually going to have a resurgence here.

Bradley J. Monk, MD: My goal because, like you all, I like maintenance and I like targeted therapy, is to have every patient have an opportunity to get bevacizumab and PARP, and maybe even together. And how do I do that? I work under the umbrella of the labels because that informs reimbursement.

There are, Tom Herzog, some rare instances though where I’ll see a patient, PARP and bevacizumab naive, who has a platinum-sensitive relapse, even though bevacizumab works after bevacizumab. How do you make that decision in the platinum-sensitive relapse, in the targeted-therapy naive, bevacizumab versus PARP?

Thomas J. Herzog, MD: I think that is difficult. This is a quickly changing landscape too because while we see 40%, 50% of the patients getting bevacizumab in the front line, there’s a decent chance they may not receive bevacizumab. There’s going to be less of a chance in the near future where they won’t have received a PARP. So that could reverse things a little bit, and I may be more inclined then to go with bevacizumab if they haven’t had bevacizumab. But also, I’ve always looked at whether they have pleural effusion, ascites, anything like that because bevacizumab does a terrific job on those patients. I’m always anxious to put those patients on.

You then turn the corners on that, if they’re naive. You also have that window of opportunity hypothesis, right? That’s the only time that you can use a PARP on these patients because if you go down the line of treatment, you won’t be able to do that. And so I look at that opportunity as well, and I look at what that might mean in terms of a lost opportunity. Because I can always bring bevacizumab in. We know from the AURELIA data how wonderful bevacizumab works in the platinum-resistant setting as well. You always have the opportunity for bevacizumab, you don’t always have the opportunity for PARP, especially if they don’t have a germline or somatic mutation.

Bradley J. Monk, MD: Yes, Sharon and Tom Krivak, does that resonate with you that if you have a platinum-sensitive patient who’s responding, really that may be the only opportunity for PARP unless they have a molecular signature? So you should capitalize on it because they might be an exceptional responder.

Thomas C. Krivak, MD:I love bevacizumab and platinum-sensitive recurrence, though sometimes I get off the highway and venture into the weeds. Like Katie, I like carboplatin/Doxil q4 every 4 weeks and bevacizumab q2 every 2 weeks. You increase the response rate and try to get a complete response and then switch them over to a PARP at that point. I then try to see how long they’ll last on the PARP again. I try to do HRD [homologous recombination deficiency] testing at times to let me see how long that that PARP duration may be. I’ve done that quite commonly. I love carboplatin/Doxil q4 every weeks and bevacizumab q2 every 2 weeks, try to get a complete response or get the best response after 6 to 8 courses, and then switch them over to PARP.

Bradley J. Monk, MD: Thank you for that. And it’s not just the schedule, it’s the adverse effect profile because you have less alopecia and less neuropathy.

Transcript edited for clarity.