Case 2: Adding Bevacizumab to Chemotherapy in Ovarian Cancer

Shannon Westin, MD: Let’s move on to the second case because this is a similar up-front patient, but with a little bit different case.

Thomas C. Krivak, MD: This is a patient here, she has a BRCA mutation, she has high-volume disease, newly diagnosed ovarian cancer. It says she’s 69-years-young, Caucasian; she went to the emergency department and had shortness of breath. She has mild hypertension and diabetes, everything is medically managed, and she is morbidly obese. She has large volume ascites. CT scan of the chest shows large bilateral pulmonary effusions but no pulmonary embolism. CT scan shows peritoneal carcinomatosis as well as bilateral adnexal masses. CA-125 [cancer antigen 125] is 525U/mL. She undergoes a thoracentesis, which is 1500 cc; cytology showed a high-grade adenocarcinoma. Paracentesis, 4500 cc, high-grade adenocarcinoma. Core biopsy of the omentum shows a high-grade serous carcinoma. The patient underwent debulking surgery with incomplete cytoreduction, so suboptimal debulked, and she’s being anticoagulated. You can see her molecular testing: TP53+, PAX8+, WT1 and CX7+, as well as a BRCA2 mutation.

What are the pros and cons in deciding whether to add bevacizumab to primary chemotherapy for this patient? We’ve talked about this in the past.

Shannon Westin, MD: You’ve talked about how you would add it to most. This is a population, and I don’t want to speak for Chad, but the 2 of us were saying that, for stage IV bulky disease, this is a population for which I would talk and consider bevacizumab because that’s where we get our biggest bang for our buck.

Chad Hamilton, MD: You can talk for me. I agree totally.

Thomas C. Krivak, MD: Would you guys have done a primary debulking? I’m not going to lie to you: 4500 cc, 1500 cc, peritoneal carcinomatosis. I don’t want to criticize, I don’t know who did the surgery, but this is somebody for whom one size doesn’t fit all, and that’s what we’re learning. They did a core biopsy and had a high-grade serous carcinoma. I don’t know. I probably would have treated this patient with neoadjuvant chemotherapy.

Chad Hamilton, MD: Yes, it was interesting. I was reading through the case, and I thought that was where this case was going. That’s where my head was going.

Shannon Westin, MD: Me, too. I would consider it. We use a lot of laparoscopy to assess these patients, to try to determine if there’s going to be a futile laparotomy. For a decently sized pleural effusion, we move more toward neoadjuvant, especially if there’s a lot of bulky peritoneal disease as well. But no judgment.

Thomas C. Krivak, MD: No judgment at all. I did those surgeries, but I try to not do them at this point. She was treated with carboplatin/Taxol [paclitaxel] and bevacizumab, and she achieved a complete remission, which is great with a BRCA mutation. Options for maintenance therapy and what influences the decision at this point: Chad had a nice discussion about the NCCN [National Comprehensive Cancer Network] guidelines. This patient has to be treated or at least be offered, and I would strongly encourage her to be on some type of maintenance therapy. She was already started on bevacizumab. I would have probably switched maintenance with this patient and had her on bevacizumab to get the improved response, and then switched over to olaparib by itself. Based off that presentation at SGO [Society of Gynecologic Oncology Annual Meeting on Women’s Cancer], I’m feeling much more comfortable about taking and adding bevacizumab with olaparib and doing a PAOLA trial approach to this patient as well.

Shannon Westin, MD: Yes, those are both viable options. You’ve got great benefit with the addition of a PARP inhibitor to bevacizumab in this case. I’ve always been a little reticent to stop bevacizumab based on some of the data on ovarian as well some other cancer types like colorectal, where there seems to be a bounce back if you stop it. The PAOLA data gave us a nice support for potentially combining both. Then, if the patient develops any kind of adverse events, you can always back down to just the PARP inhibitor if you feel like the combination is not tolerable. That’s what I would lean toward at this point.

Chad Hamilton, MD: Yes, I would agree entirely. I’m reticent to stop bevacizumab once started. This is a great patient for whom PAOLA allows us, with evidence now, to treat with a combination. Shannon described perfectly the way I would approach this.

Thomas C. Krivak, MD:The main influence is probably the high-volume disease, the pleural effusions and the ascites, and that the bevacizumab, for stage IV, will definitely help with that. Which combination would you guys use: bevacizumab for a year and then olaparib an additional year, or would you go 2 years because PRIMA used 3 years? SOLO and PAOLA were more on the 2 years. I’m curious because I’m a big fan of 3 years because 80% of these recurrences occur within the first 3 years. That was my thinking behind some of it, but there are very bright people who are designing these trials. I’m curious what you guys think about the 2 versus 3 years.

Chad Hamilton, MD: Wow, you’re forward thinking. I don’t know that I get that far out in my mindset, my approach. This is another situation where some of the trials were designed with the end points, or where do we draw the line? We have to stop it at some point without a whole lot of science to back up when to do that. I don’t have a fixed approach with when I stop it. If I’m following the guidelines in 1 trial, I will stick with that for the most part.

Shannon Westin, MD: We haven’t gotten there with many patients yet with just the SOLO-1 data, but I’ve generally been offering them to stop at 2 years. I’ll do something similar with PAOLA, but with that being said, I have some patients who were on bevacizumab maintenance that, when we got to that 15-month point, they said, “Dr Westin, I don’t want to stop,” and I said “OK.” I’ve got a few patients who have been on it for years, and they’re tolerating it well, so we keep going. I don’t think we’re ever cookie-cutter, but I will definitely offer them the opportunity to stop it at some point.

Transcript edited for clarity.