Chad A. Hamilton, MD, and Robert W. Holloway, MD, review the case of a 57-year-old woman with stage IIIA high-grade epithelial ovarian cancer.
Chad A. Hamilton, MD: Let’s jump into a case. I’ll get your perspectives on how some of this plays into your management of this hypothetical patient. Let’s say you have a 57-year-old woman who received neoadjuvant chemotherapy, and you give her carbo-Taxol [carboplatin, paclitaxel] and bevacizumab for what was a stage IIIA high-grade epithelial ovarian cancer. She initially presented with abdominal pain and unintentional weight loss. She had a left ovarian mass on exam confirmed by imaging. A CT scan also demonstrated the mass with some pelvic and inguinal adenopathy but not extensive disease and no pleural effusion. She had a paracentesis for some ascites that confirmed high-grade epithelial ovarian cancer. Germline molecular testing demonstrated HRD [homologous recombinant deficiency]–positive BRCA wild type and an elevated CA-125 [cancer antigen 125]. She had an excellent performance status. After completion of neoadjuvant chemotherapy, she had platelets of 125,000 per mm3 and hemoglobin of 9.0g/dL, which recovered a couple of months after chemotherapy completion. Then she underwent surgical debulking with complete resection of disease and had a complete response to treatment.
That’s a lot to package into that case. Let’s go back to our original thoughts. We talked about frontline treatment in the abstract. How do those things we talked about play into this case?
Robert W. Holloway, MD: One point you brought up was in frontline therapy, making a decision whether you’re going to use bevacizumab. In this case, I wonder about the decision because they didn’t describe a lot of bulky disease. With the inguinal nodes making it extra peritoneal, kind of a stage IV patient, I didn’t know if that’s why we did it. I typically use bevacizumab in instances where we have bulky upper downward disease, parenchymal, lung or liver. Clearly, it’s been show in stage IV in neoadjuvant chemotherapy that being as aggressive as you can makes a difference. In this case it was used. My only hesitation with bevacizumab in a neoadjuvant approach is potentially wound healing, and I’ve had some issues with vaginal cuff dehiscence, or just slow healing of the cuff, and I’ve had to reclose a cuff or 2 along the way.
If I use a neoadjuvant, there are a couple of problems: No. 1, if you put a subclavian port in, you can’t use a defer cycle. You have to let them heal, so you’re going to go without it. That leaves you with cycle 2. If I give cycle 3 and then I operate in 28 days, you’re right on the cusp of that. I’ve had the experience with probably 4 or 5 patients with whom I’ve had slow-healing, ischemic-looking vaginal cuffs. I don’t usually see that on open surgery, so I’m wondering about that. Then there’s the issue of having a slow-healing cuff. If I’m doing a low rectal anastomosis, am I compromising that? I haven’t had any leaks, knock on wood, in those patients, but it does worry me a little. In this case, everything went fine; she got a complete response.
I have a saying with the fellows: I don’t get off the horse that’s winning. It looks like she got a great response with this combination with bevacizumab. We’ve gotten her down to maintenance therapy. What are the options? She’s HRD wild type, so she could go on to bevacizumab plus olaparib from the NCCN [National Comprehensive Cancer Network] Guidelines and the PAOLA-1 trial, or she can go on single-agent niraparib within the guidelines. Either would provide a benefit for this patient, but I tend to not alter from what got us here. I wonder if bevacizumab didn’t drive a lot of the response with the platinum. I’d be inclined to consider that she’s healing from her surgery, reinitiating bevacizumab while the bone marrow is recovering and then add olaparib at some point.
I took the time to look at the hazard ratios in this HRD and BRCA wild type and do a cross-study comparison, which I know is fraught with problems. The PRIMA trial with niraparib had higher-risk patients for failure than PAOLA-1 or SOLO1. But if you look at hazard ratios, and they’re supposed to correct that thing, the hazard ratio for this HRD and BRCA wild-type group was favorable for bevacizumab plus olaparib. The problem is that it’s cross studied with 2 different populations, higher risk and niraparib. But because you got the patient here into remission, it’s rational to use bevacizumab with carbo-Taxol [carboplatin, paclitaxel] to continue that in your maintenance phase and add the olaparib because she’s HRD positive.
Chad A. Hamilton, MD: What I was hearing from you early on in the case is, that typically, you reserve bevacizumab for our most challenging patients: those with bulky disease and pleural effusions and who we have less of a chance of completely cytoreducing. If you start them with bevacizumab, and they end up having a homologous recombination deficiency, then stick with that regimen—layering on the olaparib with PAOLA-1 that’s got the indication for maintenance—and do prolonged bevacizumab-plus-olaparib maintenance.
Transcript edited for clarity.