Therapeutic Strategies in Advanced Ovarian Cancer - Episode 12
Transcript: Bradley J. Monk, MD, FACS, FACOG: I want to ask all 4 of you a complicated question. I want to know what the role of molecular signature is in determining what you should do in platinum-sensitive relapse. I’m going to assume that the patient has not had bevacizumab. I think it becomes simpler when the patients have had frontline bevacizumab. At the 2018 ASCO Annual Meeting, there’s a study from Italy that shows that bevacizumab after bevacizumab has a 3-month improvement in progression-free survival. With the historical experience, the approval will be bevacizumab. Then, when you get platinum maintenance, you’re going to get a PARP inhibitor. But in a patient who hasn’t had frontline bevacizumab, what role does the molecular signature play in triaging over bevacizumab as maintenance or PARP as maintenance?
Oliver Dorigo, MD, PhD: This is a great question, but we still have to kind of wrap our heads around it. I tend to get somatic mutation testing on patients who have recurrent disease before I start treating. I think the information about the genomic alterations is important. Patients who have had no germline mutations, in the BRCA1/2 genes, for example, are found in about 7%, 8% of cases to still harbor the somatic BRCA mutation and, therefore, could be a candidate for PARP inhibition.
Bradley J. Monk, MD, FACS, FACOG: Do you use more PARP or less PARP in the BRCA patient?
Oliver Dorigo, MD, PhD: I do more PARP in patients who have either a germline or a somatic mutation.
Bradley J. Monk, MD, FACS, FACOG: Really? Do you use more or less PARP in the BRCA patient?
Leslie M. Randall, MD, MAS: I use PARP whenever I can. If I have a platinum-sensitive PR/CR, I’m using PARP.
Bradley J. Monk, MD, FACS, FACOG: Thank you for that. I actually use less.
Oliver Dorigo, MD, PhD: Do you use an adjunctive dose?
Bradley J. Monk, MD, FACS, FACOG: No. That’s also true, but I preferentially triage the bevacizumab in the BRCA patient because I can use PARP in treatment. You’ve got 1 chance to use PARP in that nonmolecular signature patient, and it’s now. She might have a durable response even though she doesn’t have the molecular signature, so you’ve got 1 chance. In the mutated patient, you have a chance down the road.
Do you use more or less PARP in the BRCA-mutated patient for maintenance in platinum-sensitive disease?
Thomas Herzog, MD: I tend to use it in that group. I also use it in the group that is wild-type and mutant negative, because it’s the only chance I’ll have.
Bradley J. Monk, MD, FACS, FACOG: But if you have to make a decision between bevacizumab and PARP, how?
Thomas Herzog, MD: I look at other factors. Do they have any significant ascites?
Bradley J. Monk, MD, FACS, FACOG: Good point.
Thomas Herzog, MD: Do they have a pleural effusion? I think bevacizumab works particularly well in that area, and so I sort of look at that as being some selection bias toward bevacizumab. That’s what I do. I tend to use more of the PARP now instead of bevacizumab in that setting. I think I can use bevacizumab later on. I can use it again if it’s been long enough. Or, if they happen to recur within 6 months, I can use it in the platinum-resistant setting. So, I’ll be able to get them bevacizumab, but I won’t be able to get them a PARP inhibitor if they’re HRD—normal and have the BRCA wild-type gene.
Bradley J. Monk, MD, FACS, FACOG: Katie?
Kathleen Moore, MD: I’m most similar to Tom. The GOG-0213 data clearly showed us that no response rate isn’t as important as longevity, but it is important if you’re trying to get someone to maintenance. And so, you increase your response rate tremendously with bevacizumab. You have these high-volume recurrences, pleural effusion, ascites. I’m much more likely to use bevacizumab in that setting. I do struggle with this question for someone without those features. Then, what am I picking in the maintenance setting? I like the ARIEL2 data, but I’m struck by the fact that the duration of response is just about 12 months, if I’m remembering correctly, in a BRCA patient.
Bradley J. Monk, MD, FACS, FACOG: In treatment.
Kathleen Moore, MD: In treatment. If I give that patient chemotherapy and put her into complete response and then put her on maintenance, cross-trial comparisons are unfair. If you look at any of the studies, the point from finishing chemotherapy to recurrence is 18 to 20 months. That sounds a lot different to me.
Bradley J. Monk, MD, FACS, FACOG: I understand. Does this resonate with you? In the nonmolecular signature, whether it’s HRD or BRCA, the response to platinum…if you don’t use PARP now, you’re never going to have another opportunity. What I’m trying to begin to brand is the one-shot. You’ve got 1 shot to get the PARP into this patient. Does that resonate with you, or not really? In the molecular signature—negative patient, where bevacizumab is an option, do you preferentially triage to PARP because it’s their only opportunity?
Kathleen Moore, MD: I hope that it’s not going to be their only opportunity.
Bradley J. Monk, MD, FACS, FACOG: But it’s likely.
Kathleen Moore, MD: We have data that demonstrate that in the treatment of biomarker-negative patients, there’s clinical benefit with PARP inhibitor use.
Bradley J. Monk, MD, FACS, FACOG: But it’s off-label, so you can’t really say that.
Kathleen Moore, MD: No, I can’t say that.
Transcript Edited for Clarity