RTP On Demand: Current and Future Role of PARP Inhibitors in the Management of Ovarian Cancer (Video Program) - Video 8A 54-year-old woman undergoes optimal debulking surgery, experiences disease progression through multiple lines of chemotherapy and is determined to have BRCA-positive disease
5:43 minutes.
TRANSCRIPTION:
DR HERZOG: I had a 54-year-old woman who came in, not an atypical situation in the sense that she was searching for something else in terms of what’s out there. So it was really a consult after I moved to Cincinnati. And she had originally had a Stage IIIC high-grade serous cancer, was operated on. She had optimal debulking but had some small miliary disease that was present that was widely distributed in the op note in terms of residual that was left. She was treated with carboplatin and paclitaxel, IV. She received 6 cycles, had a complete response both by physical exam, imaging and chemical response by her CA-125, which had been originally elevated. It returned to normal. I think her nadir was somewhere in the neighborhood of 10 to 14, somewhere in there. And it was 11 months later she had a CA-125 that spiked up. She was found to have a positive supraclavicular node. This triggered a PET CT that also found abdominal pelvic disease that was widespread. She then underwent treatment with carboplatinum and pegylated liposomal doxorubicin. She received 6 cycles, and her CA-125 returned to a nadir of 17 at that point. And then it was 7 months later that she received carboplatinum and gemcitabine again for a CA-125 that elevated up to 266, so she had 3 successive CA-125s, first checked every 3 months then every month times 2. And it went up to 266, so they started carboplatinum and gemcitabine on her. After that plateaued, she then wanted to know what could she do next. She’s now 3 months in and she presents with some abdominal bloating, a small fluid wave that was confirmed on imaging with moderate ascites, and a rising CA-125. Interestingly, fairly young woman, but she had not been tested for BRCA status at that point. So we went ahead and tested her. She was BRCA-positive. Fortunately, olaparib had just come on the market, so we were able to get her on that. So she was on the olaparib capsules. We started a little less than 3 months ago, and so far she’s had a good response. Her CA-125 values have decreased nicely, but they’re not falling a whole lot more. I think she went from 44 to 42 over the last one. So whether she’s going to go further down or not, I don't know. But that’s where she stands right now. The good news is that in terms of her symptoms, she’s not having any symptoms. She’s eating normally again. Her fluid wave has resolved, and, overall, she’s doing well. DR LOVE: Would you say you see evidence of an objective response, or maybe not yet? DR HERZOG: Yes. I mean, I think she’s probably due for a scan. We usually wait a few months. I would bet that if we use RECIST criteria, there’s a good chance she has a partial response. DR LOVE: And she was BRCA1 or 2? DR HERZOG: She was BRCA1. DR LOVE: I want to ask you a couple more questions about her treatment, but just to stay on the BRCA thing, what is her family situation? And what kind of counseling did you initiate within the family? DR HERZOG: That’s tricky and really gets into who even does the genetic counseling. In this case, I’m at a cancer center. We were able to get her to a genetic counselor in a fairly timely fashion. It all worked out. In fact, we have an express route worked out for our patients who are under consideration for therapeutics. So that’s a different scenario than if you’re just being tested for the sake of being tested. And so there’re lots of reasons to test, right? So you’re going to help this particular patient, inform her as to her prognosis, so it has prognostic value. It has therapeutic value. And then, very importantly and what you bring up here, is the implications for the whole family. And that’s a real important part of this. And we let the genetic counselors handle that aspect of it. But a real problem is that we don’t have enough genetic counselors. And so we’re looking at surrogate ways of getting this done. Should we be testing tumor and reflexing then to germline testing blood? Should we be just doing germline testing on the blood and then reflexing to genetic counseling if there’s a variant of undetermined significance or if they’re positive? And so there’s a lot of ways to consider this. But I do think whoever’s doing that original testing does need a modicum of knowledge about this field. Otherwise, you can get into trouble in a hurry. DR LOVE: Do you think that it is reasonable for, let’s say, a physician in community-based practice, who doesn’t have the genetic counselor that you do, to try to do a brief genetic counseling themselves, or do you think it’s really — DR HERZOG: Yes. DR LOVE: — necessary to go to a genetic counselor, at least to draw the BRCA? I mean, once they’re positive is another issue, but to draw the BRCA? DR HERZOG: Right. Well, it’s a tough answer to give you. I personally feel that genetic counselors add a tremendous amount in terms of the resources that they bring to the table. However, I just got done telling you that we don’t have enough genetic counselors to get all this done in a timely fashion. So I think if we know what the goals are — and they’re finite — in terms of, “I want to know if this patient can go on a PARP inhibitor at this time” — it may be more reasonable in some cases to have that done at point of care and then reflex the testing if they’re positive. The other thing I would say, though, is that the person providing that initial counseling should have some knowledge of all this themselves. |