new drug for Trip Negs

Lisa 39

I cannot open this article. It requires registration and subscription. Is it possible that you could paste the article? thanks

Am I missing something?  Has the link changed?  Here's what I got:

There's nothing about triple negative, a little about ixabepalone (Iressa), but mostly about endocrine positve treatments in the metastatic setting.

Brenda

Maintaining Quality of Life in Patients With Refractory Metastatic Breast Cancer: An Expert Interview With Dr. Martine Piccart

Posted 10/21/2008

Mary Beth Nierengarten, MA
Author Information

Editor's Note:

Despite the many cytotoxic agents, such as the taxanes and anthracyclines, that are available to treat metastatic breast cancer, resistance to these agents will develop in some women that will require other therapies. Ideally, such therapies will maintain quality of life, while prolonging progression-free and overall survival. This is also true for the many women who receive endocrine therapy as first-line treatment for their metastatic disease but in whom resistance to these therapies will invariably develop.

Ongoing discussion about optimizing treatment in this setting includes controversial issues such as the relative efficacy of single-agent sequential therapy vs combination therapy; in whom to use bevacizumab; and, appropriate use of new agents such as ixabepilone, an epothilone analog approved in October 2007 by the United States Food and Drug Administration for treatment of refractory metastatic disease.

To discuss some of these issues, Mary Beth Nierengarten, MA, on behalf of Medscape Oncology, spoke with Martine Piccart, MD, PhD, Professor, Chief, Department of Medicine, Jules Bordet Institute, Brussels, Belgium, shortly after the 2008 Breast Cancer Symposium that was held in Washington, DC, in early September.

Medscape: I understand that you participated as a panelist for a tumor board on metastatic breast cancer during the recent Breast Cancer Symposium in Washington DC. What were some of the key issues brought to you and discussed by the panel regarding treatment for patients with refractory metastatic disease?

Martine Piccart, MD, PhD: The second case presented to the tumor board was a patient with advanced HER2-positive breast cancer who had previously been treated with an anthracycline, a taxane, and trastuzumab and who now had progressive disease. The question was what do you give next?

This case generated a great deal of discussion among the panel members about what is available in this type of situation. We all agreed that the data at this moment are strongest for the combination of capecitabine and lapatinib, based on a randomized trial of approximately 400 patients that found an advantage with combination capecitabine and lapatinib when compared with capecitabine alone.^[1] On the other hand, a smaller study in Europe in a somewhat less heavily pretreated population progressing on trastuzumab showed an advantage for the combination of continued trastuzumab and capecitabine compared with capecitabine alone.^[2]

So our first choice for this patient is the combination of capectabine and lapatinib.

Medscape: Was there any further discussion on the issue of giving single-agent therapy vs combination therapy in patients with metastatic disease who fail their initial front-line treatments?

Dr. Piccart: That issue came up with the first patient we discussed -- a young woman with hormone-receptor-positive metastatic disease. This case was well selected because it helped the panel of experts make the point that for women with hormone-receptor-positive metastatic breast cancer, endocrine therapy, in most situations, would be the first choice. When I say most situations, I am referring to women who do not need a very rapid shrinkage of their tumors.

Although oncologists tend to believe that outcomes will be better with chemotherapy, clinical trials have never shown that survival is improved when chemotherapy is used as first-line treatment.

So if you can start with endocrine treatment, it can be incredibly effective for a long time and it also preserves quality of life better than chemotherapy.

All the experts on the panel agreed that endocrine treatment should be the first choice for this young woman who presented with breast cancer metastatic to bone and with a primary tumor that expressed hormone receptors.

Notably, about two thirds of those attending the panel discussion agreed with that choice, but there still were about one third of physicians who would select chemotherapy first.

It was also interesting to see that experts on the panel from the United States and Europe all agreed that endocrine therapy was the first choice for this woman with disease limited to the breast and bone.

Medscape: Could patient age have something to do with that choice?

Dr. Piccart: No. A young patient with an endocrine-responsive tumor has a higher chance of benefiting from an endocrine treatment. There is a misconception that if you are young, you need chemotherapy. There is no need to rush chemotherapy in advanced disease. There is time to observe the patient to see how she responds to endocrine therapy. When a response is seen, it is usually of longer duration than that seen with chemotherapy.

Medscape: You said that this case generated a discussion on the relative benefits of single-agent sequential therapy vs combination therapy?

Dr. Piccart: Yes, all patients who are treated with endocrine therapy will, at a certain point, become resistant to endocrine therapy. At that point, we introduce chemotherapy and need to consider 2 important questions. The first is whether to use single-agent or combination therapy, which is very controversial. The second, which we did not discuss extensively but is very interesting because of the differences in opinion among oncologists, is whether patients should receive bevacizumab in addition to chemotherapy.

In terms of choosing between single-agent and combination [therapy], the panel favored the use of single-agent therapy at the optimal dose unless the clinical situation is dire and requires an extremely rapid response such as, for example, in the case of symptomatic lung disease.

In metastatic breast cancer, you often don't need an objective response. In other words, you don't have to shrink the tumor because, in most cases, shrinkage will not benefit the patient. What you need to do is freeze or stop the tumor from growing while preserving quality of life for as long as possible.

The emphasis here is on the need in metastatic breast cancer to stabilize the disease as soon as possible. In metastatic breast cancer, you often don't need an objective response. In other words, you don't have to shrink the tumor because, in most cases, shrinkage will not benefit the patient. What you need to do is freeze or stop the tumor from growing while preserving quality of life for as long as possible. This means that you don't often need very aggressive regimens because, even though they confer a higher response rate, they don't translate into improved survival and they increase toxicity and cost.

Medscape: Do oncologists recognize that the goal of therapy in the metastatic setting is stabilization rather than tumor shrinkage?

Dr. Piccart: I don't know. I still see oncologists who prefer to use these aggressive combinations. But I favor single agents because I think they are easier to administer, the toxicity is easier to manage, and survival is not compromised.

The use of bevacizumab in this setting is also controversial. We now have 2 randomized controlled trials, the ECOG^[3] and the AVADO^[4] trials, which are positive for the added benefit of bevacizumab.

What is striking to me is that the benefit seen in these 2 trials in terms of response rates and time to disease progression does not translate into a survival benefit. Neither trial shows a survival benefit for the combination of bevacizumab with chemotherapy. Also, the magnitude of benefit is much larger in the ECOG trial than in the AVADO study, a finding that nobody can explain.

Based on these data, I'm not going to routinely use this expensive drug in metastatic breast cancer. The benefit for patients, namely achieving objective response (eg, tumor shrinkage) is something you only need in selected women. So if you have a situation where you do not need to shrink the tumor, I would not prescribe bevacizumab. Of course we are able to control side effects of the drug most of the time, but I don't think we should offer this agent to everybody. This is, of course, a very controversial issue.

Medscape: What do you think of some of the new drugs in the pipeline, or of newly available drugs such as ixabepilone, which has received [US Food and Drug Administration] FDA approval for treatment of refractory metastatic breast cancer?

Dr. Piccart: First of all, it is always good news when new active agents are discovered. I think, however, that a distinction needs to be made between drugs that show a dramatic improvement in patients with advanced breast cancer and drugs that offer a statistically significant but clinically modest benefit to patients.

For example, the trial that lead to FDA approval for ixabepilone showed that combination ixabepilone with capecitabine conferred a better response than standard treatment with capecitabine alone in anthracycline- and taxane-refractory patients with metastatic breast cancer.^[5] So the combination therapy was able to shrink the tumor more often and was associated with a slightly better progression-free survival. However, the advantage was really modest and the data were too immature to evaluate overall survival.

To me, it is interesting to consider using a treatment such as ixabepilone earlier in the course of disease, where cure is possible. Adjuvant use of this agent may be particularly interesting, and those studies are ongoing.

Regarding use of these drugs in women with advanced breast cancer, I think we have to be a bit critical and selective. In the end, capecitabine plus ixabepilone did not prolong survival, and toxicity was increased in this trial. Ultimately, I think that this combination should only be used when rapid shrinkage is required for a tumor that is causing very severe symptoms. If shrinkage can ameliorate these symptoms, then the combination regimen should be considered.

In all other situations I would still use the oral single agent capecitabine, which keeps patients out of the hospital.

The experts on the metastatic breast cancer tumor board panel were all in agreement on this despite the positive results from the ixabepilone trial.^[5] The bottom line is that we all agreed that we would use the combination treatment only in selected patients.

Medscape: Is there anything else you may like to add about new therapies in development?

Dr. Piccart: Another interesting issue related to ixabepilone, which is currently under investigation, is that there appears to be a gene signature that can predict which patients will benefit from the drug.^[6] Researchers have found that this signature is present mostly in patients with triple-negative breast cancer, meaning breast cancer that is devoid of hormone receptors and not overexpressing the HER2 receptor.

We badly need new drugs for these patients who rapidly exhaust all of the standard chemotherapy options and it seems like ixabepilone could represent a drug of particular interest to women with this type of breast cancer. The good news is that there are now clinical trials underway trying to demonstrate this.^[7,8] This is an interesting development.

Medscape: Are you hopeful about the new therapies and treatment options for patients with refractory metastatic breast cancer?

Dr. Piccart: Yes, I am quite optimistic. I think there are likely going to be advances based on some new and exciting knowledge coming from the laboratory and from some very preliminary clinical observations.

I think that how we look at and treat breast cancer is undergoing a revolution. Breast cancer seems more and more like multiple diseases rather than 1 disease. We are already increasingly making this distinction in early breast cancer and I think it is also true in metastatic disease.

Currently, the treatment of advanced breast cancer is largely based on the characteristics of the primary tumor. So when a patient comes in with metastatic breast disease, you go back and look at the characteristics of the primary tumor, such as whether it is hormone receptor positive or over-expresses HER2, and then you choose your therapy.

What I think may change in the coming years is that physicians will understand the need to get tissue whenever possible because of a growing awareness that the biological characteristics of the disease can evolve. A good example of this is that a few tumors that were originally HER2-negative can become HER2-positive at the time of metastases.

What is also fascinating is the study of circulating cancer cells in the blood and our current efforts to better characterize them. I think this could eventually bring new therapies in the future.

So if we discover new targets on these cells and if we can differentiate which circulating cancer cells are clinically relevant and are really going to impact on patient outcome, then it will be possible to attack metastatic breast cancer earlier and more efficiently.

To me, these are the most exciting research areas that are likely to bring significant progress in the coming years.

This activity is supported by an independent educational grant from Bristol-Myers Squibb.

FlaLady, believe me that I pray for your quick response on Ixempra every single day. You're never far from my thoughts.

Love,

Annie

Thanks Annie & Tender,

I've had a couple of bad weeks and could not figure out why I had such bad headaches and nausea.  I've never been nausea on chemo.  (not with all 9 different chemos and 40+ tx's) I finally realized what I had done to myself.  I started using the Nicotine patch to see if it would help control my neuropathy.  Well...I had a allergic reaction to the nicotine patch.  After a few days off this D%*M patch a feel better.  Main side effect is fatigue and a little more issues with the neuropathy.

Flalady