Case 3: Second-Line Therapy for Recurrent Ovarian Cancer

Chad Hamilton, MD: We’re going to change pace here a bit and move to a case of recurrent ovarian cancer, platinum-sensitive. This is a 58-year-young, in Tom’s words, female, diagnosed with stage IV ovarian cancer, high-grade, serous. She is BRCA1-mutated, CA-125 [cancer antigen 125] elevated at 460 U/mL. She underwent suboptimal debulking: residual disease of a centimeter and a half. She received IV [intravenous] carboplatin and Taxol [paclitaxel], achieved a partial remission, and then was continued on olaparib maintenance. Twelve months later, her symptoms returned, a multifocal recurrence within the abdominal cavity. CA-125 again elevated, good performance status. She received another 6 cycles of carboplatin/Taxol [paclitaxel], this time with bevacizumab added, and she achieved a good partial response. CA-125 is decreased but still slightly elevated at 45 U/mL.

I’m going to open these questions up for a bit of panel discussion. Do you agree with the second-line choice there, the treatment with carboplatin/Taxol [paclitaxel]/bevacizumab? If one of you could take up the discussion of what about secondary cytoreduction or re-resection? Why don’t we start there, and then we’ll move through these questions as we go. Tom, do you want to take a first stab at this?

Thomas C. Krivak, MD: Yes. I’m assuming she progressed on olaparib, which is disappointing, but it is going to occur at times. The second line of therapy is fine. Carboplatin/Taxol [paclitaxel]/bevacizumab, carboplatin/Doxil [doxorubicin]/bevacizumab, and carboplatin/gemcitabine/bevacizumab are all good. Those are all good, and maintenance is going to be answered. We’re fortunate to have Shannon on because she’s instrumental in designing these PARP-after-PARP inhibitor questions that are going to need to be addressed, and this is a classic case for that.

I’m going to go off into the weeds a bit and say that for re-resection, we do consider that because this patient is young and healthy. I know that the secondary surgical cytoreduction with [Robert] Coleman, [MD], great study, great GOG [Gynecologic Oncology Group] trial, didn’t show a benefit, but BRCA patients are sometimes a bit different. I’m considering re-resection, and I know that HIPEC [hyperthermic intraperitoneal chemotherapy] is controversial at best, but there’s also a role for that, and we need to come up with biomarkers for that.

There’s the textbook answer, and then there are the options. I would present to this patient that she didn’t receive IV/IP [intraperitoneal] chemotherapy, that there is consideration of a re-resection, consideration for IV/IP [intraperitoneal] chemotherapy treatment in the recurrent setting, as well as HIPEC. I know that those are all controversial, and saying those around a bunch of fellows, there would be a lot of criticism from fellows and faculty, but in the appropriately selected patient, I’d consider that. It’s not standard of care. I agree with what they did, but I also think that you had additional options for those folks. If I had to make a choice, I would be on the arguing side that I would re-resect this patient. If somebody said, “Do you want to be pro or con,” I would have no problem being on the pro side, knowing that I have an uphill battle with data to overcome.

Chad Hamilton, MD: Do you like bevacizumab in this circumstance too?

Thomas C. Krivak, MD: Yes, I would do bevacizumab in this circumstance. Clinical trials are the number 1 thing. We have to answer the question of PARP-after-PARP, there’s no doubt about it; that’s going to be important. This patient progressed on PARP, so the utility of PARP in that instance is probably going to be a bit different. We don’t yet know what can re-sensitize to PARP. It was fascinating at last year’s NRG [NRG Oncology semiannual meeting], it was a great debate you guys had, and then providing quite a few combination therapies. This is an area of investigation. A clinical trial would definitely be high on the list. I thought their choice was fine, but patients at times get referred to some people because they’ll operate. I would actually say that is not a great option, but if you want to go outside the box, I would consider it.

Transcript edited for clarity.