Considerations for Managing Recurrent Ovarian Cancer

Thomas Krivak, MD:One of the things I always teach when I talk with the residents and everybody is: Responders respond. There’s this group of patients that we may have treated for 6, 8, 10 years, and it seems like each time they come in, they respond. You’re going to have that group of patients that, to me, will do well. They’ll have a durable response. Then, unfortunately, you have these patients that will develop a recurrence, and so they may have had a treatment-free interval of 12 to 16 months, and then their second treatment was just 2 months, but then they’re progressing on each of these lines of therapy.

I think both of those patients are a little bit different, but looking at the newer data that are coming out, I would have to say that that’s the big thing. If you look at this patient who is diagnosed in 2014, now we’re in 2019. We have a whole host of different clinical trials that are available, as well as these clinical trials that have led to ability for us to use these other agents. I think in this patient and focusing on PARP inhibition today as they go along in their treatment, she didn’t receive PARP inhibition up front, and she received bevacizumab in the second or third line, that this would be a patient that we’d want to test them molecularly to see; I know that we have a germline that was negative, but we could test more accurately to see if there’s a somaticBRCAmutation, or you could elect to send the patient’s tumor off to Myriad, which does the myChoice, which is the HRD [homologous recombination deficiency] test.

Or you could potentially choose to send that patient’s tumor to Foundation Medicine, which does an LOH [loss of heterozygosity] test, which is similar but not the same. I think one of the key points is, when you look at the QUADRA data, you look at the PRIMA data, they are using the Myriad test. I think that when we’re talking about how we’re testing patients and we’re seeing this patient may have this genetic alteration, we really need to define what test we’re using to make sure that everybody’s on the same page, since there are different testing modalities and different types of commercial tests out there.

I can see patients going up to 6, 7 lines of therapy. I think sequencing chemotherapy has become very challenging in that you have your platinum-eligible patients that will get repeat platinum doublets, possibly with bevacizumab, to get a response, and then get switch maintenance to PARP inhibition. Those patients will do very well. As you go up further-line therapies, it’s hard to say how those patients are going to do. I think when we get up in the further-line therapies, you want to look at agents that may be less toxic, that are easier to deliver, to try not to have a significant decrement on their quality of life.

I would have to say if we look at the percentage of patients who are becoming eligible for that fourth, fifth, sixth line of chemotherapy in the United States, where we treat patients very aggressively, I would say that a number of those patients are increasing.

In general, when I kind of lecture on how to take care of an ovarian cancer patient, kind of from initial diagnosis to potentially—you know, unfortunately—enrolling in that patient in hospice care, one of my thoughts is—I try to talk with the residents that I’m working with—is that you want to make sure and get a quality surgery for those patients, at least 1 quality surgery for those patients.

Again, if they’re young and very functional, I try to give them IV/IP [intravenous/intraperitoneal] chemotherapy like this patient had. Some people don’t believe in that treatment anymore, but they need a platinum doublet. Unfortunately, when these patients recur, I think before a patient would eventually end up in the hospice, they really should receive a PARP inhibitor, Avastin, as well as immunotherapy.

These patients that have these durable responses, I could see them being on treatment for a significant period of time, then combinations of what we just talked about: niraparib with bevacizumab; niraparib with immunotherapy. I think are other options down the line that we may be able to safely deliver to these folks.

I think the percentage of patients living to the fourth, fifth, sixth line is there. Those are conversations we have to have with our patients. Some patients are deconditioned at that time, and they may not feel like they want further therapy. On the QUADRA trial, you saw it was opened up in 20-some odd sites, and they accrued 460 patients. These patients are all greater than third-line therapy to get that. A significant portion of these patients were 6-line or greater. I think it’s going to be something that we see more and more often as we take this disease from an acute illness to a chronic disease, and we’re trying to manage it with medications to help prevent the cancer from growing or coming back.

I think for this patient, again, she was wild-type for germline. I want to test the tumor. You know for this patient, if she had HRD positivity, because you know the new QUADRA data are HRD positive and platinum sensitive, you can go ahead and treat those patients with single-agent niraparib, and I think that that would be a fine choice at this time. The patient had been treated with combination IV/IP chemotherapy; she had received bevacizumab. She received platinum doublets once again. I would have to look at quality of life and say, “Is this somebody that we could use the QUADRA data for, which would be single-agent niraparib? Or is this somebody that, you know—are they functional and want to try something else if they’re not HRD positive and not germline?” I think the TOPACIO data, which are combination immunotherapy with niraparib in a highly platinum-resistant patient population, had 65% disease control rates. To me that was amazing. In a lot of these patients, we may try different ways of starting single-agent and then use in combination to see if we can get a response for them. A lot of it will depend upon their functional status. In this patient’s case, she had an excellent functional status. She’s young with a functional status, an ECOG status of 0, meaning we’re going to try to be as aggressive as possible.

Transcript edited for clarity.

Case: A 58-Year-Old Female With Heavily Pretreated Recurrent Ovarian Cancer

H & P

• 58-year-old female diagnosed in 2014 with stage IV ovarian cancer
  • Pathology: high-grade serous carcinoma, epithelial ovarian cancer
  • CA-125: 460 U/mL
  • CT with contrast of the pelvis, abdomen, and chest revealed a 4-cm mass in the left ovary and peritoneal carcinomatosis
  • Patient underwent suboptimal debulking surgery; residual disease 1.5 cm
  • Received IV/IP carboplatin/paclitaxel (6 cycles); achieved complete remission
• 2 years later (2016) symptoms returned; CA 125, 255 U/mL; ECOG: 1
  • Received carboplatin/paclitaxel (6 cycles) and bevacizumab; achieved good partial remission; CA 125, 45 U/mL; continued on bevacizumab maintenance
• 1.5-years following second-line therapy (2017), again presented with symptoms; CA 125, 550 U/mL; ECOG: 0
  • Genetic testing;gBRCA1/2wild-type
  • Received carboplatin/gemcitabine (6 cycles); CA 125, 46 U/mL; achieved complete remission
• Currently:
  • CA 125, 620 U/mL
  • CT shows several small masses in the lung left lower lobe (largest is 3 cm)
  • ECOG: 0