The Role of PARP Inhibitors in Ovarian Cancer - Episode 3
Frontline Treatment and Neoadjuvant Chemotherapy
Expert physicians and pharmacists consider the frontline treatment approach, with special consideration of the roleo f frontline neoadjuvant chemotherapy in treating individuals with ovarian cancer.
Maurie Markman, MD: Now we're going to turn our attention to antineoplastic therapy and then on to the PARPs [poly ADP ribose polymerase inhibitors]. To begin this conversation, I'm going to ask Mike to say a little bit about frontline therapy. What's your preferred regimen?
Michael Birrer, MD, PhD: We've had a lot of changes over the last 5 years in terms of treatment, but to a certain extent, sort of the gold standard I think remains the same, which is this is a carboplatin/paclitaxel doublet. I prefer carboplatin with an AUC [area under the curve] calculation of 6. I don't think 5 is wrong. The Europeans use it more than we do. But my standard is 6, and paclitaxel at 175 mg/m2. And I'm a Q3 week [every 3 weeks] kind of guy. As you know, there was a Japanese study, J-GOG that showed weekly paclitaxel was maybe a little bit better tolerated and more effective. But since then we've had a randomized trial that show they're really equivalent. So more often than not, I think we're still using Q3 weekly regimen. The new changes, which we'll get to, is, when do you put in BEV [bevacizumab]? Now with the recent 2019 ESMO [European Society for Medical Oncology annual meeting] reports in the studies, how do you work PARPs into this?
Maurie Markman, MD: Do you want to make any comment at all about IP [intraperitoneal] therapy?
Michael Birrer, MD, PhD: Yes. I'll give the historic perspective and then Wendel can chime in because I know he still uses it quite a bit. Historically, there ahve been randomized trials showing IP is more effective than IV [intravenous]. The most recent study was GOG-252, which is a complex study. I'm not sure how much we can interpret from it, but all the arms, IP versus IV, were equivalent. So my sense is in the community, IP is slowing falling out of favor. But certainly at centers and academic centers who are comfortable with it, it's still being used. Wendel, do you want to comment on it?
R. Wendel Naumann, MD: I think we've had 3 trials. They've all shown survival advantage, including your trial of GOG-114, Maurie. I think it fell out of favor with GPG-252, but there's still a role for this therapy. Particularly I think the benefit for IP therapy is probably driven by patients who have BRCA mutations. And that's where we use it based on some of the data that we have from our institution.
Maurie Markman, MD: Another major issue in the area of management of ovarian cancer is the role of so-called neoadjuvant chemotherapy, and of course, now that ties into what one might do after chemotherapy and surgery. Wendel, what is neoadjuvant chemotherapy and what do you think the role is?
R. Wendel Naumann, MD: Neoadjuvant chemotherapy is where we give 3 cycles of chemotherapy, usually 3 cycles of chemotherapy before surgery. I think the role of this has changed. We now have 4 randomized trials that have shown that neoadjuvant chemotherapy is a reasonable approach for patients with advanced disease, that there’s no detriment in terms of outcome with neoadjuvant chemotherapy. And the surgery can be done with less morbidity and a greater success rate in terms of optimal surgical resection. There are people who still like primary surgery, and again, as Mike says, this is not wrong. I think though if you have somebody with advanced disease, we generally lean toward neoadjuvant chemotherapy more than primary surgical debulking.
Maurie Markman, MD: Mike, any comment?
Michael Birrer, MD, PhD: Well, I think the last statistics I saw, it’s up around 50%, 60% in this country. In Europe it’s probably even higher, and I think a lot of it, as Wendel said, is it makes the surgery actually a little bit easier after 3 cycles. From a physician/scientist standpoint, I like it in that we now get tissue that’s been exposed to chemotherapy. We can ask a lot of interesting questions about that, so that’s an additional benefit. It’s here to stay. I don’t see it changing, but as pointed out, primary debulking is perfectly reasonable, too.
Maurie Markman, MD: I guess one way of concluding, there is potentially no downside of giving neoadjuvant chemotherapy if you think there’s a risk of surgery. But if you can do the surgery safely, that is the decision of the surgeon.
R. Wendel Naumann, MD: That’s a great point though. If you look at the SCORPION trial, very skilled surgeons and a good optimal surgical resection rate, but the 30-day mortality in that trial is 8%. So I think that’s something that we have to keep in mind.
- Ovarian Cancer Overview
- Ovarian Cancer Diagnostic Process