|
||||||||
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
| Tracks 1-22 | ||||||||||||||||||||||||||||||||||||||||||||||
|
Select Excerpts from the Interview
Tracks 5-12
DR LOVE: For a patient like this, what would you have considered for
adjuvant chemotherapy?
DR VOGEL: That’s a difficult question to answer until we obtain the results
from NSABP-B-38 (2.1). Currently, the two major contenders are TAC and
dose-dense AC followed by paclitaxel. Those regimens are close in terms of
their efficacy in clinical trials (Citron 2003; Martin 2005). The major difference
is that in a prospectively defined subset analysis, TAC was statistically
significantly better than FAC for patients with hormone receptor-positive
disease (Martin 2005).
The problem is that this is a third-generation versus a second-generation protocol. And the data with dose-dense AC followed by paclitaxel are third-generation versus third-generation. However, the CALGB trials have not shown a statistically significant benefit from this regimen for patients with hormone receptor-positive disease. A benefit exists, but it is not statistically significant (Berry 2006). If I were to be a purist and go with the data, I would probably use TAC. I believe that most US oncologists would use dose-dense AC followed by paclitaxel.
DR LOVE: What are your thoughts about Bill Gradishar’s randomized Phase II
trial comparing weekly nab paclitaxel to every three-week docetaxel?
DR VOGEL: Weekly nab paclitaxel showed better activity, with approximately
double the response rate (Gradishar 2006b, 2007; [2.2]). Investigators
are trying to mount a major trial in the US because much of this trial
was conducted outside of the US. However, I’ve been impressed with the
European and South American investigators, and I believe they had enough
control over those trials to make them viable. If those data hold up, then nab paclitaxel could become the dominant taxane.
DR LOVE: For this patient who had a local recurrence in the axilla about a
year after adjuvant dose-dense AC
nab paclitaxel, what would you consider
in terms of chemotherapy, and would you consider bevacizumab?
DR VOGEL: I would be considering bevacizumab. Because she finished her
adjuvant chemotherapy more than a year ago, I might be tempted to go back
and treat her with nab paclitaxel and bevacizumab.
DR LOVE: This patient was enrolled in a study with the UCLA network in
which she received docetaxel and bevacizumab. She had a good response
— tumor shrinkage and symptom improvement.
How are you approaching the decision about using bevacizumab for women with metastatic breast cancer? How do you make the decision about which agent to combine it with, specifically when a relapse quickly follows paclitaxel?
DR VOGEL: We were fortunate to participate in the RIBBON 1 trial, and
many of our patients were enrolled in that trial. RIBBON 1 allowed an
anthracycline, nab paclitaxel, docetaxel or capecitabine. Before the XCaliBr
trial results (Sledge 2007; [2.3]), from the standpoint of quality of life and
given the choice of these different agents, I was choosing capecitabine.
I use a lot of capecitabine in my practice, but I wasn’t impressed with the results for the eight or nine patients whom I treated with capecitabine/bevacizumab. Most of the patients in the RIBBON 1 trial were allowed to cross over to open-label bevacizumab.
So you could then move to second-line nab paclitaxel or paclitaxel, if you wished, with open-label bevacizumab. I did that, and most of my patients who crossed over to the taxane/bevacizumab have fared nicely.
I have one or two of my original patients still on capecitabine/bevacizumab. However, I view the XCaliBr trial as a relatively negative trial (Sledge 2007; [2.3]).
The interesting part of the trial — an unexpected finding — was that the patients with hormone receptor-positive disease seemed to do much better than those with hormone receptor-negative disease when treated with capecitabine/bevacizumab (Sledge 2007; [2.3]).
Tracks 13-17
DR LOVE: When you are making this decision in a clinical setting, how
do you think it through?
DR VOGEL: This woman had a positive node, which puts her at a somewhat
greater risk. If I had a patient with a good-risk, node-negative tumor who was
having symptoms with an aromatase inhibitor, I would probably take her off.
If she was tolerating the aromatase inhibitor, I would discuss the question of
delayed relapse. If this particular patient were tolerating the drug well, I would
encourage her to participate in NSABP-B-42. As part of the informed consent
process, patients usually declare which way they want to go.
DR LOVE: What has been your experience with the arthralgias associated with
the aromatase inhibitors (2.4)?
DR VOGEL: It’s highly variable. Approximately 30 percent of my patients
have to be switched to another therapy or discontinue the aromatase inhibitor.
Aman Buzdar and I had an agreement not to agree. He told me, “It is a class
effect. If you get it with one aromatase inhibitor, you will get it with another.”
I absolutely do not agree because I have seen patients respond to a second
aromatase inhibitor.
DR LOVE: Does it make a difference if it is steroidal or nonsteroidal?
DR VOGEL: No. I see no rhyme or reason. If you take any one of them and
have a problem, you can switch to one of the others, and the patients can sail
through it.
DR LOVE: What percent of those 30 percent do you end up having to take off
aromatase inhibitors?
DR VOGEL: I’d say approximately five percent.
DR LOVE: Is there a typical clinical pattern or set of complaints that people
tell you about?
DR VOGEL: Not really. It can occur in any joint, more frequently in the
fingers and toes. I’ve had some patients who have been on exemestane develop
what sounds like paresthesias, which I haven’t heard about with the nonsteroidals.
That makes that toxicity pattern a little different.
Tracks 18, 21
DR VOGEL: I would treat this patient with adjuvant chemotherapy and
trastuzumab, but we don’t have much data in this area. The only source of
data is BCIRG 006 (Slamon 2006) because they allowed patients with small,
node-negative, HER2-positive tumors.
So we have data with TCH, which includes carboplatin. If you’re thinking “inside the box” and you intend to treat, then it would be with TCH. If you were thinking “outside the box,” an interesting combination would be docetaxel/cyclophosphamide and trastuzumab.
DR LOVE: How do you feel about the new NSABP/CIRG study — the
BETH trial — evaluating TCH (docetaxel/carboplatin/trastuzumab) with or
without bevacizumab (2.5)?
DR VOGEL: I will be participating in that trial. I do have concerns about the
brain and brain metastases in these patients. A study from Poland obtained an
MRI of the brain from 80 patients with HER2-positive breast cancer.
Thirty-six percent of the MRIs were positive for brain metastases (Niwinska 2007). We have data with lapatinib suggesting that perhaps it could provide some protection in the brain. That story must play out over the next few years.
In the ALTTO trial (2.6), you have the advantage in several of the arms of learning whether you can reduce brain metastases with lapatinib in patients with HER2-positive disease. I would have loved to have another randomization in the BETH trial to lapatinib or no lapatinib, after the other therapies were completed.
 |
 |
EDITOR'S NOTE
Survivors
Neil Love, MD
- Select publications
INTERVIEWS
Ian E Smith, MD
- Select publications
Charles L Vogel, MD
- Select publications
Sandra M Swain, MD
- Select publications
Paul E Goss, MD, PhD
- Select publications
Hannah M Linden, MD
- Select publications
Breast Cancer Update:
A CME Audio Series and Activity
 |
 |
 |
 |
 |
