INTERVIEW WITH DR. MARK PEGRAM

DR. LOVE: I want to dissect out a little bit about how you approach the HER2-positive, ER-positive patient with metastatic disease. But first, as a baseline, so I can see your overall strategy of treatment, how do you approach the ER-positive, HER2-negative woman with metastatic disease? Then we can compare?

DR. PEGRAM: Well, in light of the published results by Jean-Marc Nabholtz in JCO last year and in light of the results of the Arimidex adjuvant trials presented at this meeting, there's strong, compelling evidence now to use aromatase inhibitors first-line in ER-positive metastatic disease. There is even strong evidence to use it as adjuvant therapy in ER-positive disease, even before metastasis now.

DR. LOVE: I'm trying to dissect out - and, of course, that's in postmenopausal women.

DR. PEGRAM: Mm-hmm.

DR. LOVE: When you see an ER-positive woman with metastatic disease, what's your thought process in terms of choosing between hormonal therapy and chemotherapy?

DR. PEGRAM: That really boils down to clinical judgment, and those decisions really have to be made on a case-by-case basis. The old school of this decision tree and what used to appear in tables and distinguished textbooks of oncology, was that patients with ER-positive visceral disease you treat those with chemotherapy, and non-visceral disease, you treat with hormonal therapy. It turns out that it is not quite that simple. There are good data now showing that visceral ER-positive disease certainly has a response to hormonal therapy, and it's not an absolute exclusion. So, really, you have to take each patient individually. Obviously, the elderly patient with smoldering low-volume, bone-only ER-positive disease, it's really easy in those cases to do an aromatase inhibitor treatment up front. Whereas, a young patient with a weakly ER-positive disease and rising LFT's or tachypnea with exertion, in those patients I'm much more concerned and I want a fast response. There, I am much more likely to be aggressive with a chemotherapy regimen, even a chemo-combination regimen with Herceptin in the HER2-positive cases.

DR. LOVE: Okay. Well, we're still on HER2-negative.

DR. PEGRAM: HER2-negative is the same thing. I'm going to use chemotherapy in the aggressive relapse.

DR. LOVE: Your decision tree sounds a lot like most research people.

DR. PEGRAM: It's the same as everybody else's.

DR. LOVE: It sounds like the NCCN guidelines, which basically…

DR. PEGRAM: Sure.

DR. LOVE: …for an ER-positive patient use hormone therapy, unless it's rapidly progressed, visceral disease, et cetera.

DR. PEGRAM: Sure.

DR. LOVE: Okay. So, that's your baseline for the ER-positive, HER2-negative.

DR. PEGRAM: Mm-hmm.

DR. LOVE: Now, what about the ER-positive, HER2-positive patient?

DR. PEGRAM: Well, our situation is a little bit different, being in an academic center. I target those patients for the ongoing hormone therapy Herceptin clinical trials, because that way we can get an answer. I'm really struck, though, I must admit, by the data presented by Chuck Vogel, with single-agent Herceptin. I'm very struck by the survival advantage in the pivotal Herceptin-chemotherapy trial, that Herceptin-based treatment can be associated with prolonged survival in advanced disease. So, in HER2-positive cases, I'm really going to take a hard, long look at Herceptin early on.
If you look at the survival data from Dr. Vogel's single-agent Herceptin trial, the survival looks almost identical to the chemotherapy plus Herceptin pivotal trial results. If you look at the demographics of the patients, they were very, very similar, surprisingly similar. These are not randomized trials. I'm making dangerous cross-trial comparisons. I'll admit that. But, I'm struck that there may be a survival advantage to Herceptin-based treatment in HER2-positive patients, and I'm going to consider that early on. I'm also going to consider adding hormonal therapy to it in the ER-positive cases, which, as I mentioned, doesn't happen very often. This doesn't come up very commonly in the clinic. But, when it does, I am going to consider Herceptin early.
Like many other investigators and colleagues, in patients with really low-volume ER-positive disease, if you can watch them closely, if they don't live a great distance and you're not worried about them getting lost to follow up, it would be reasonable to give them a trial of hormonal therapy. In the absence of a rapid response, then move on quickly to Herceptin-based therapy for those HER2-positive cases.

DR. LOVE: Now, I'm trying to factor in the fact that you're from Los Angeles and you're on the cutting edge of everything here.

DR. PEGRAM: Well, my opinion is different than many of my distinguished colleagues, and that opinion is just due to my comfort level in prescribing Herceptin. I've been prescribing Herceptin since about 1991, and so it's a little bit easier for me to recommend it for HER2-positive patients, because I'm comfortable with it. For many practicing clinicians and even other researchers at other institutions who weren't involved in the Herceptin registration trials, they're not used to it. They're less comfortable. It's not their default thinking yet. I don't think they've necessarily looked at the comparisons between the Vogel data and the Slamon New England Journal data set. I think once all of these data sets are out there and people have a chance to study them closely, more and more people will be considering Herceptin as the basis for treatment in HER2-positive cases. That's my opinion.

DR. LOVE: That's interesting and it may be that this algorithm you're talking about is going to be the algorithm a couple of years from now, five years from now. There's got to be somebody thinking about this first. But, again, I'm just trying to dissect out, understanding that your position may be quite a bit different than other people, your thoughts on this. So, if you have a woman who has ER-positive, HER2-positive disease, are you generally going to use hormone therapy? Then the question is whether you're going to give Herceptin in addition to that?

DR. PEGRAM: I will say, in my opinion, it's the other way around. I'm going to give Herceptin and decide whether or not to give them hormone therapy. And I almost always will, because of the lack of side effects of hormonal therapy in breast cancer. I'm struck by the synergistic result with tamoxifen and Herceptin by the Yale group, by Rich Pietras' data on tamoxifen-Herceptin in vivo, in animal models, and the more recent data looking at Faslodex-Herceptin in vivo with striking interaction there. So, this concept of Herceptin-hormonal therapy is sound. It's a very logical way to go. And I'm going to consider that combination up-front, off study early on in patients with ER-positive, HER2-positive disease.

DR. LOVE: It's interesting, this spectrum of viewpoints that you see in oncology, both in the community and the research setting. It was interesting, too, to see how people responded to the ATAC data. You saw all of these philosophies coming out. Some people want to see the final study published and end results before they take action, and others who were ready to take action. You know, we're talking about laboratory data here.

DR. PEGRAM: Well, your point is well taken. For the practicing clinician, it certainly does pay to be skeptical. It's important to realize that San Antonio and ASCO are abstract presentations. This is preliminary data. None of this is the final data. Clinicians in the audience are very sophisticated. They are well aware that they are just eyeballing, getting an early peek sometimes of data sets. Many of them have had the experience of seeing results from the next ASCO that have had the opposite conclusions. I think being skeptical is very healthy. People should challenge the data. That's why it's being presented at big meetings like this. This is not being presented to change anyone's standard of care in the audience. It's being presented for criticism and for debate. It's got to stand the test of time. That's what makes for all the excitement at these types of meetings.

DR. LOVE: That's what oncology is all about. That's what medicine's all about, but particularly oncology. I think the other thing that really is vexing for an oncologist is to bypass an opportunity for a patient. If you wait six months before you apply some type of adjuvant data and it does turn out that everything pans out and doesn't get reversed, the patients that you've treated during the six months that you've waited have lost an opportunity. So, that really is the challenge of oncology.

DR. PEGRAM: Exactly. It's really the magnitude of the benefit of, let's say, a study result. If the magnitude of the benefit is small and, even though it may be statistically significant, I think it's wise to challenge those results and wait to see if it stands the test of time.
If the magnitude of the benefit is enormous, then I'm much more eager to act in my own clinical practice and will change my standard of practice sooner than some more conservative colleagues on the basis of preliminary data. But that's okay. It is important to recognize, and I think everyone who views abstract presentations realizes it's not the P value that's important. It's the magnitude of the clinical beneficial effect that's important in looking at preliminary data.

Previous | Continue

Page 4 of 5

Home · Search