Thomas Krivak, MD:I think in 2019, if this patient would come into the office today, and knowing what we know about the case, I would say that we’d look and we’d say this patient is stage IV. I think many of us would talk about chemotherapy first, interval debulking, chemotherapy, and then maintenance treatment. With the newer studies showing that PARP maintenance is an important part of that, we would want to do genetic testing. Genetic testing would include looking at the germline status.
We would have the patient see us in the office, talk about chemotherapy, talk about surgery, talk about TT [targeted therapy] guided biopsy to get the patient ready for neoadjuvant chemotherapy. An important part would be having her either see a genetic counselor within the office, or sometimes we’ll have to do that type of counseling within the office, because they may not be available to come back. I would recommend some type of panel test to look for any type of genetic predisposition for ovarian cancer. That’s very important for this patient in that it’s going to help direct her treatments, because I think the treatment has changed since 2014, when this patient presented.
If this patient had a germlineBRCAmutation, she would get chemotherapy, surgery, chemotherapy, and then would receive maintenance therapy with a PARP inhibitor at that point.
If she would get genetically tested, there have been many PARP inhibitor studies that have been recently reported.
SOLO-1 looked at patients with advanced-staged ovarian cancer treated with maintenance olaparib. Most recently at ESMO [European Society for Medical Oncology], a study reported by Tesaro/GSK [GlaxoSmithKline] was the PRIMA trial looking at single-agent niraparib for patients with germline mutations, as well as all-comers in another study, PAOLA, that looked at this as well.
In today’s 2019 management, we want to know what the germline status is, and then a lot of us would send the tumor off for tumor testing to look for tumor genetic alterations inBRCA1andBRCA2, and some of us would look for what is called genomic instability, or HRD [homologous recombination deficiency]. Based off of those test results, you may triage this patient to a different maintenance strategy at that point.
The strategy that we’re using now…and I think that this is very complex, because the results of the ESMO trialsthe SOLO-1 trial the PAOLA trial—as well as the PRIMA trial all showed clinical benefit. Really, SOLO-1 was with germline mutation patients and somatic mutation patients. When we’re in the wild-type realm, it really boils down to: Do clinicians believe in what’s called homologous recombination deficiency, or HRD testing?
Personally, I do. I think the HRD test is another way to look and try to capture more patients who may benefit from maintenance therapy. The 2 trials did show that in the HRD-positive patients, those that had the genomic instability type of score, that those patients benefited either from single-agent niraparib or a combination of olaparib and bevacizumab. I look at the patients who have a germline mutation or somatic mutation ofBRCA 1orBRCA 2. I would give them chemotherapy and surgery, and then they would be treated with PARP maintenance, whether it’s olaparib or niraparib. Then the patients who were noted to beBRCAwild-typetest their tumor. Again, if their tumor is positive, that’s a somatic mutation; they would get single-agent niraparib or olaparib. if those were negative, then you look for the HRD testing. If the patients are HRD positive, what many of us are doing, we’re going with single-agent niraparib, some people would use the combination of olaparib and bevacizumab. It’s very confusing because you can see the same group of patients choosing 2 different potential regimens. Then, in the HRD-proficient patients, or the ones that have a score that shows that their tumor does not have any deficiency, most of us would say we should probably be using niraparib in that group, and then saving bevacizumab for possibly later.
I’ve looked at some of these data. I think that if you would ask 4 or 5 different treating medical oncologists as well as GY [gynecologic] oncologists, that you may get different interpretations of the data, and I think it’s going to take us a few years to try to figure out how to use this up-front testing. Is combination therapy better than single-agent therapy, or is really single-agent therapy the way to go? Then we’re not using our bevacizumab at this time, and we can potentially use that for, unfortunately, when these patients recur. Because as you go through this case, as we know, unfortunately, the majority of these patients with ovarian cancer have advanced stage disease. Ultimately, they’ll recur, and with that recurrence, we want to make sure and have more treatment options available at that time.
Transcript edited for clarity.
Case: A 58-Year-Old Female With Heavily Pretreated Recurrent Ovarian Cancer
H & P