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You are here: Home: BCU 6|2002: Supplement: Melody A Cobleigh,
MD
DR MELODY COBLEIGH
DR COBLEIGH: That’s
correct. We do not have a prospective, randomized trial, but this
is one of those situations where I think I would like to use my
best clinical judgment. I certainly have never lost a patient whom
I started on Herceptin as a single agent. If the patient is progressing,
you can always add the chemotherapy. The difference between Herceptin
and hormonal treatment is you don’t have to wait six weeks
or eight weeks to find out if it works. When Herceptin works, it
works very, very quickly, often within a couple of weeks. So if
it’s a patient who does not have life-threatening disease,
I don’t think you’d lose anything by giving them a month
of Herceptin and see how things are going.
DR LOVE: That’s interesting. When you talk
about not having life-threatening disease is that the same kind
of criteria you’re looking at in the ER-positive patient?
DR COBLEIGH: Exactly
the same criteria. In other words, if you’ve got some time,
take it slowly, do it the benign way, and see what you get.
DR LOVE: When you do start Herceptin whether it’s
alone or with chemotherapy, first of all, I assume you continue
at least until the patient progresses?
DR COBLEIGH: Yes.
DR LOVE: And, what about beyond that?
DR COBLEIGH: In terms
of using Herceptin, as long as it works.
DR LOVE: Let’s say you start the patient
on Herceptin and chemotherapy and then they are progressing, do
you stop both or do you just switch the chemotherapy?
DR COBLEIGH: So if
a patient’s on combination chemotherapy plus Herceptin, what
do I do when a patient progresses? As you know, there isn’t
any information on this in terms of clinical trials, but one of
the things that has consistently been true in the Herceptin story
is that the laboratory models have predicted what was happening
in the clinic. And what the laboratory models show us is that Herceptin
when combined with most chemotherapeutic agents is more effective
than when a chemotherapeutic agent is used alone. So I err on the
side of expense because I believe the laboratory information. Until
I see a trial that shows me that this is not true, I do continue
the Herceptin along with the chemotherapy.
DR LOVE: Do you continue it indefinitely as long
as you are actively treating the patient, or do you stop at some
point?
DR COBLEIGH: I continue
it indefinitely.
DR LOVE: In the patient who has life-threatening
disease and you want to use chemotherapy, what drug do you tend
to use?
DR COBLEIGH: If the
patient hasn’t seen a taxane previously, I would use Taxol
plus Herceptin.
DR LOVE: And the next chemotherapeutic agent you
would use?
DR COBLEIGH: Navelbine.
DR LOVE: There is a trial now that’s going
to compare the two? Any gut feeling about the relative efficacy?
DR COBLEIGH: They
probably will be identical.
DR LOVE: Let’s go over to the ER-positive
side of the equation. ER-positive, HER2-positive, how do you approach
those patients granted there aren’t that many?
DR COBLEIGH: Again,
if you have time, you can take the benign path. I would start that
patient, if she was premenopausal on tamoxifen, and if she was postmenopausal
on an aromatase inhibitor. If she progressed, then I would add Herceptin.
DR LOVE: And continue the hormonal therapy?
DR COBLEIGH: Yes.
DR LOVE: Let’s say she responded to the
hormone and then progressed, and you wanted to use another hormone,
would you keep the Herceptin going?
DR COBLEIGH: Yes.
DR LOVE: One of the things that always comes up
is the 43-year-old, ten-node-positive, HER2-positive patient. There’s
the question of using adjuvant Herceptin off protocol in a situation
like that, any thoughts?
DR COBLEIGH: I haven’t
done it. Since the clinical trials started I’ve only been
putting patients on the clinical trials, and I certainly have had
patients go elsewhere to get Herceptin off protocol. I think that
the bone marrow transplant situation taught us a lot, and we really
need to get this answer quickly. We had preconceived notions about
how transplant would work and now we know. So that’s my policy.
DR LOVE: Inflammatory breast cancer?
DR COBLEIGH: We have
a clinical trial that uses Herceptin with inflammatory breast cancer,
so in the context of that clinical trial, we do use it.
DR LOVE: What is the trial? Who’s doing
it? What phase is the trial?
DR COBLEIGH: It’s
uses induction Herceptin plus Taxol for 12 weeks followed by AC
for 4 cycles, followed by definitive therapy, followed by Herceptin
plus radiation therapy.
DR LOVE: So it’s a Phase II?
DR COBLEIGH: It’s
a Phase II study.
DR LOVE: What about Stage IV NED, a patient who
has her mets taken out and they are HER2-positive?
DR COBLEIGH: (Pause)
I would not treat that patient. Again, because it’s tough
to improve upon the asymptomatic patient. The reason why I hesitated
is because I have seen a couple of patients with local-regional
recurrences who were HER2 amplified, and in that situation the standard
of care would be to remove the node and radiate. Nobody knows what
to do after that, whether to give them chemotherapy or not. In those
patients I have used Herceptin plus chemotherapy followed by Herceptin
plus radiation, and then stopped the Herceptin. In other words,
I’ve thrown the book at them. One of them I met about two
years ago and she’s doing fine. The other one I met about
a year ago and she’s doing fine.
DR LOVE: Any thoughts in terms of the optimal
schedule of delivering Herceptin?
DR COBLEIGH: Every
three weeks.
DR LOVE: That’s it, end of sentence.
DR COBLEIGH: End
of sentence. It’s not FDA approved, but the data are there,
and I think it will be eventually approved by ODAC (Oncologic Drugs
Advisory Committee). It’s so much easier on patients and it
just makes so much sense.
DR LOVE: Any other issues about Herceptin that
you’d like to bring up, mistakes to see being made in the
community or things you disagree with?
DR COBLEIGH: Well,
I like to call this Larry Einhorn phenomenon. Larry was the one
who basically came up with the regimen that cured testicular cancer.
What happened after that was he rarely saw a de novo testicular
cancer anymore; he just saw the failures. I think that there are
some very important questions that are about to be asked in HER2-positive
patients. The trials are designed such that these patients have
to have been Herceptin naïve. It would be a real shame if this
resource were not placed in the clinical trials. For example it
looks like there is a connection between the HER1 and HER2 pathways
and there is a study that is being initiated by ECOG that’s
looking at the combination of Iressa and Herceptin. It’s a
very important study. But we see very few untreated HER2-positive
patients anymore.
Another concept that is extremely important is the idea that there
appears to be a connection between the HER2 pathway and the angiogenesis
pathway. So a trial that is about to be initiated is looking at
the combination of Herceptin and anti-VEGF. Again, these people
have to be naïve to Herceptin. So, I guess my hope is that
patients will become aware of these trials, the doctors will become
aware of these trials. It’s such a small percentage of patients
and that they will enter them into these clinical trials or if they
are not available, physicians will refer them specifically for that
trial. Not that you would send the patient forever, but just for
the purposes of these trials that are asking novel questions.
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