DR PEREZ: The patient had diffuse liver mets. There were 5 different ones, and they were between 1 and 1 1/2 centimeters in size.
DR LOVE: Interesting situation. She’s asymptomatic yet has significant liver disease. Nothing else?
DR PEREZ: Nothing else. Yes.
DR LOVE: Ruth, what would you be thinking?
DR O'REGAN: I think the key things for this lady — I mean, I know the liver mets are definitely an issue, but the key thing of the study is she’s 7 years since her diagnosis. She’s 2 years off anastrozole. So I have to say I would use an endocrine approach, just an endocrine agent alone. Fulvestrant or tamoxifen would be reasonable for this patient, I think. Watch her very closely. And just because she’s got liver mets doesn’t necessarily lead me down a chemo route, unless I think she’s really in some kind of danger of getting into real trouble. And I think she’s got a very good chance of responding well to endocrine therapy, given her profile.
DR LOVE: What about repeating the anastrozole or letrozole?
DR O'REGAN: I probably wouldn’t do that. I mean, she’s been off it 2 years only. That probably wouldn’t be my first choice, I have to say.
DR LOVE: Bill?
DR GRADISHAR: I agree. I think that in this patient you have a window where you could try a different endocrine therapy, watch her closely. I would not come back to what she had previously been on. I would choose something else. And if she responded, great. If not, then she would go down the chemotherapy path.
DR LOVE: Sara?
DR HURVITZ: I would not do chemotherapy. I try not to be frightened by visceral metastases unless there’s truly a crisis where a patient’s enzymes are abnormal. I would consider an AI in combination with fulvestrant and/or fulvestrant at a higher dose — so taking a different approach, though there’s no evidence that she’s truly AI resistant.
DR LOVE: AI and fulvestrant. In what situations do you think about that?
DR HURVITZ: I do not use it in patients who’ve been treated with tamoxifen. I think that there is some subset data from the 2 studies that were done that patients who are tamoxifen pretreated may not be as sensitive to the combination. I use it primarily in the up-front setting, similar to how the SWOG study was done.
DR LOVE: Hope, what would you be thinking about with this patient?
DR RUGO: Based on the data that we have right now, we don’t know that it matters which hormone treatment we give. We had the small first trial data that suggested that higher-dose fulvestrant, our standard dose now, versus anastrozole, was superior. But that’s a small Phase II trial. So I think that the one downside of giving fulvestrant is you have to come in for injections, but you don’t have to comply with the pill. So there’s advantages on either side.
I wouldn’t use everolimus because it’s not the setting in which it was approved right now. But I do think that there was very exciting data presented at San Antonio about a cyclin-dependent kinase inhibitor, referred to as 991 because it has no other name. And that drug showed a rather remarkable difference in progression-free survival and will be tested in a Phase III trial opening in the next few months.
DR LOVE: Lisa, what would you be thinking about with this patient? And what do you think about Sara’s idea of an AI and fulvestrant? In what situations do you use that?
DR CAREY: I think the first question, of course, is: What are you going to use first — chemo versus endocrine therapy? And to be honest, I think we tend to underplay the role of biology here. And I suspect that if you were to do a randomized study in visceral disease, hormone receptor-positive, HER2-negative and first line, you may get the same responsiveness to chemotherapy in up-front hormone therapy in patients who are not on any drug when they started. So, again, you can’t improve on being asymptomatic. And clearly endocrine therapy is better tolerated, and I would lead with an endocrine agent, as I think everybody has said. I tend to downplay visceral involvement as a variable in deciding that.
DR LOVE: And what about the idea of an AI and fulvestrant?
DR CAREY: I limit combining those two to the situation where it showed a benefit. That would be completely endocrine-naïve patients, which is really a minority in our population.
The one thing I do differ on is I actually would probably go back to a nonsteroidal AI in her and try that. In a sense, the goal of therapy is very different in metastatic disease. I’m just looking for control in an asymptomatic patient. And she did very well for 5 years and had a 2-year disease-free interval. And I might go back to exactly the drug she was doing well on before.
DR BRUFSKY: I think the issue is: How confident are you that your hormone therapy will work in time to prevent her from getting LFT abnormalities? Because once her bilirubin starts to go up, it gets a lot harder to give her chemotherapy. I think that’s really the mystery. I mean, this is someone who comes in, a 7-year disease-free interval, small liver mets. I would agree. I think hormone therapy is a reasonable one.
One could be pushed to exemestane and everolimus, but on the other hand, I would agree with you that it’s been a 2-year drug-free interval. I think any hormonal therapy would be reasonable. I probably would offer hormone therapy.
DR LOVE: Now it’s time to find out what happened. How’d she get treated?
DR PEREZ: Anastrozole. It just was started recently.