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You are here: Home: BCU 6|2002: Supplement: Joyce O'Shaughnessy,
MD
DR LOVE: We did a patterns-of-care study with
100 oncologists and 100 surgeons. We basically presented cases to
them and asked them what they would do. Relevant to the two things
that you just talked about, we presented metastatic cases to them.
We did this for education purposes, not to prove a point about what
people are doing in practice. One of the things that I thought was
interesting about this Miami Meeting patterns-of-care study is relevant
to what you were saying about the use of Herceptin. We presented
a bunch of first relapse cases of HER2-positive, 3+ overexpressers.
For example, 43-year-old woman with bone mets who received prior
ACT, IHC is 3+. Guess what percent would include trastuzumab as
part of their therapy, whether alone or with chemotherapy?
DR O’SHAUGHNESSY:
Assuming she’s ER-PR-negative?
DR LOVE: Right. Would you be surprised if I said
65 percent?
DR O’SHAUGHNESSY:
Yes.
DR LOVE: I thought you would be, and if you look
through the various scenarios it varies from 65 to 85 percent. So,
what it suggests is 10-20 percent of oncologists are not routinely
using Herceptin as first-line therapy in IHC 3+ patients. Does that
surprise you?
DR O’SHAUGHNESSY: It doesn’t, Neil, because in the
Slamon paper, you’d have to read it closely to understand
that the survival advantage was quite large using Herceptin up front,
in spite of the fact that two-thirds of the patients later on got
Herceptin. So, the implications of that are – this was essentially
a crossover study. Everybody got Herceptin – not everybody
– two-thirds of women got Herceptin eventually. But there
was still a big survival advantage strongly suggesting you want
to be using it up front for your maximum survival advantage. But
that’s a bit of a fine point. I think people say, “Okay.
Herceptin’s great. It’s associated with a survival benefit.”
I think the message that you really should be using it up front
from these data to get your maximum survival advantage, I think
that’s a finer point. I’m not sure that that is as widely
appreciated.
DR LOVE: What I found, if you look at the NCCN
practice guidelines, if you talk to 20 or 100 people who focus all
their attention on breast cancer, you find almost uniformly that
people use Herceptin up front, in general. Is that your take, also?
DR O’SHAUGHNESSY:Yes.
I think so. Some folks will use it by itself, particularly in the
women that you’re talking about.
DR LOVE: Sure. Sure.
DR O’SHAUGHNESSY:
I think it’s certainly possible, for example, that if you
had someone where intravenous therapy was going to be a real problem
for them, it’s certainly possible somebody might give that
person oral Xeloda, for example, because we still have little data
combining Herceptin with Xeloda. What we have looks quite good,
but it’s really not out there yet in any major way, because
the Phase II studies are still ongoing. So, that might be an occasional
consideration. But, sure, breast cancer doctors who think about
breast cancer all the time, I will agree with you, they really will
use Herceptin up front pretty consistently. I know myself, I think
of it as a given when I’m trying to decide what chemotherapy
to give up front for HER2 overexpressers. I mean, it’s like
you’re going down a divergent pathway. It’s divergent.
HER2 overexpresser, you’ve got to do something where you’re
going to have Herceptin in there. HER2 non-overexpresser, that’s
a different decision pathway.
DR LOVE: The way I’ve heard it expressed
in the metastatic setting was, for the HER2 over-expresser, they’re
going to get Herceptin up front. The question is – are you
going to give chemotherapy or just give it alone? Is that the way
you think it through?
DR O’SHAUGHNESSY:
Yes. Yes, I sure do. That’s exactly right.
DR LOVE: The other interesting question, that
I know there’s been a lot of controversy is what do you do
with a patient who you started on Herceptin for metastatic disease
once they progress? Basically, what is your practice?
DR O’SHAUGHNESSY:
That is a situation you face every day. It’s a really good
question, because patients always ask you that. I was really impressed
with the original pivotal trial. There were some patients out there
years in stable remissions on Taxol and Herceptin. I hold that one
dear. So, what I say to women, if they’re doing well on Taxol
and Herceptin, or anything else with Herceptin, I say, “Look.
Let’s see how you’re doing. If you’re doing well
on it, I won’t stop it.” I really don’t stop it,
because on Melody Cobleigh’s study with single-agent Herceptin,
too, she had some patients out, again, for years, as I recall.
DR LOVE: Well, the other question is, what do
you do once the patient progresses?
DR O’SHAUGHNESSY:
Right.
DR LOVE: Do you continue beyond? Or at least continue
the Herceptin?
DR O’SHAUGHNESSY:
Right. Well, of course, there’s no data there, really, at
all, in my opinion, to guide us. So, what we can only do is talk
about what we’re doing. What I usually do is, when I get around
to using an agent that has shown remarkable activity in combination
with Herceptin, I use Herceptin. So, Navelbine, Taxotere, and probably,
now, Gemzar. I will give the Herceptin, because the levels of effectiveness
that you’re seeing with these combinations are much higher
than we’re used to seeing, albeit most of them are small Phase
II trials. We have to bear that in mind, although the corroborative
study that was done in Florida from Palm Beach for Navelbine-Herceptin,
it was presented at San Antonio, came in with excellent Phase II
results, just like the Dana-Farber study had shown. So, consistently,
we’re seeing very, very high anti-tumor activity with Taxol,
Taxotere and Navelbine. Now some suggestion with gemcitabine.
Neil, I think that most doctors are trying to milk all the activity
we can get out of these. Herceptin’s very well tolerated.
It’s almost like you’re not really causing harm to the
patient. Many of our chemotherapy agents are given very frequently
anyway, either weekly or – now we’re getting more comfortable
with every-three-week Herceptin. So, you don’t feel like you’re
disadvantaging the patient and you’re really hoping to get
more mileage out of these chemotherapy agents, particularly when
you get in the taxane-refractory patients. You’re down now
to response rates that are not very big. So we want to get all the
mileage we can out of them.
I’ll give you an anecdote. I am caring for a women now who
Dr Bob Livingston had treated with Taxotere, Navelbine and Herceptin
on a Phase II clinical trial. She had a fantastic response, and
a long, durable response – lung disease, only. Then she moved
to Dallas, and I inherited her. And she had progressed, unfortunately,
slow, progressive disease. I treated her with Xeloda, and she responded,
not quite as long. Then we went on to Alimta, an investigational
drug that is an antifolate. We went onto that, and she did not respond
to Alimta and was progressing. She had never had Taxol, so I decided
to give her weekly Taxol with Herceptin. She’s been in remission
two and a half years even though she had already had Herceptin.
Perhaps she would have done that with Taxol alone. We don’t
know. But my gut is that’s a darn effective combination for
her. So, we all have these anecdotes, and I think that keeps us
going. We use our clinical intuition on these things.
DR LOVE: Do you want to hear what these clinicians
had to say about metastatic disease with chemotherapy and where
XT fit in?
DR O’SHAUGHNESSY:
Yes. (Laughter)
DR LOVE: We’ll see if you can guess. I’ll
just pull a couple of numbers out here for you. For example, we
had a case we presented, 43-year-old woman with bone mets who received
prior AC, ER-negative, HER2-negative. Generally speaking, what would
you do with a patient like that?
DR O’SHAUGHNESSY:
Well, I’m thinking of a woman right now in my mind, precisely
like her. And it depends, Neil, on how extensive her disease was
and whether she was hurting. It depends on her disease-free interval.
DR LOVE: Asymptomatic bone mets.
DR O’SHAUGHNESSY:
Asymptomatic bone mets. It probably would depend a little bit on
her disease-free interval, as well. But I think, in that particular
case, I would individualize to be honest with you. If she had a
quick relapse and a lot of bony disease, even though it was asymptomatic,
I would give her XT in combination. Conversely, if she really just
had minimal disease, I might treat her with Xeloda by itself or
I might treat her with weekly Taxol or weekly Taxotere by itself.
DR LOVE: Well, what was interesting was, about
45 percent of these docs said either Taxotere or Taxol, but about
20 percent said XT. We presented the same case in a 63-year-old
woman. The exact same case and you have only a third of them saying
one of the taxanes, and nobody saying XT. I thought it was interesting,
because, to me, 63 is not that old for there to be that big of a
difference in the perception. It seems like it was the age that
was driving things.
DR O’SHAUGHNESSY:
Mm-hmm. That’s interesting. I think that’s probably
true, Neil. I think breast cancer in the forties is probably pretty
different than breast cancer in the sixties, by and large. Of course,
there’s overlap, certainly. But, by and large, cancer in the
forties is, I don’t know, perceived as more of a significant
life-threatening disease than metastatic breast cancer in the sixties.
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