About BCU CME Meetings Special Editions Meet The Professors Patterns of Care Conference Partnerships Patient Projects Other Tumor Types About us
You are here: Home: BCU 3 | 2008: Julie R Gralow, MD

Julie R Gralow, MD

Tracks 1-15
Track 1 Clinical algorithm for the treatment of metastatic breast cancer
Track 2 Combination regimens in the treatment of metastatic breast cancer
Track 3 Incorporation of nanoparticle albumin-bound (nab) paclitaxel in the treatment of breast cancer
Track 4 Proposed SWOG randomized Phase II trial of nab paclitaxel and sunitinib in locally advanced and inflammatory breast cancer
Track 5 Defining clinical trial endpoints in the investigation of anti-angiogenic agents
Track 6 Treatment of HER2-positive metastatic breast cancer
Track 7 Administration and side effects of lapatinib
Track 8 Lapatinib for HER2-positive CNS metastases
Track 9 ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trial
Track 10 Dose and schedule of capecitabine
Track 11 Clinical use of capecitabine/ bevacizumab in the treatment of metastatic breast cancer
Track 12 Incorporation of the epothilone B analog ixabepilone and capecitabine into the treatment of breast cancer
Track 13 Role of adjuvant anthracyclines in patients with HER2-positive disease
Track 14 SWOG-S0307: A Phase III study of adjuvant bisphosphonates in Stage I to III breast cancer
Track 15 Z-FAST study: Effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women receiving adjuvant letrozole

Select Excerpts from the Interview

Track 2

Arrow DR LOVE: What is your usual first-line chemotherapy regimen for a patient with metastatic breast cancer? Do you include bevacizumab?

Arrow DR GRALOW: I believe the data with a taxane/bevacizumab regimen are strong. For weekly paclitaxel/bevacizumab, a doubling in progression-free survival — in absolute terms, adding six months — is clinically meaningful (Miller 2007). So the data support using bevacizumab with weekly paclitaxel.

In the Southwest Oncology Group, we have a lot of experience with the combination of antitubulins and vinca alkaloids — either docetaxel or paclitaxel in combination with vinorelbine.

At ASCO this year, we will be presenting a Phase II study of docetaxel/vinorelbine with trastuzumab for patients with HER2-positive disease.

Docetaxel/vinorelbine is an impressive regimen, whether it’s administered in combination with bevacizumab for HER2-negative disease or with trastuzumab for HER2-positive disease. That’s my experience.

So I tend to use that as an aggressive regimen up front if I want to obtain a rapid response. We have presented data previously on docetaxel/vinorelbine without bevacizumab for patients with HER2-negative disease (Gralow 2005).

Track 3

Arrow DR LOVE: Can you review what we know about nab paclitaxel in breast cancer?

Arrow DR GRALOW: Nab paclitaxel does not require premedications, has a faster infusion time and has the ability to deliver somewhat higher doses of the drug. I believe we are seeing a dose-response effect above what we’ve traditionally observed with paclitaxel.

Certainly the data with every three-week nab paclitaxel versus paclitaxel are in favor of nab paclitaxel (Gradishar 2005; [5.3]). We have randomized Phase II data showing that when administered weekly, nab paclitaxel may be as good as, if not better than, docetaxel (Gradishar 2007).

It’s a fascinating drug, and I like using it a lot. I like not having to administer steroids and antihistamines and the markedly reduced chance of allergic reactions. I’m excited about trials moving nab paclitaxel into the adjuvant setting.

Arrow DR LOVE: What about nab paclitaxel in combination with bevacizumab?

Arrow DR GRALOW: Absolutely. When I can get insurance company approval, I will use that regimen.

Arrow DR LOVE: What do we know about that combination at this point?

Arrow DR GRALOW: We have no randomized Phase III trial data. However, we do have safety data. I make the leap that it is the same core drug — paclitaxel — at a higher dose.

I don’t see the need for a randomized Phase III trial to prove efficacy in that setting when I’m substituting a somewhat higher dose of the core drug, paclitaxel.

Track 6

Arrow DR LOVE: What about metastatic disease in the patient with a HER2-positive tumor? How would you approach such a case when the patient has received adjuvant trastuzumab?

Arrow DR GRALOW: Fortunately, we now have a second HER2-targeted agent with FDA approval. So for patients who progress on or quickly after stopping adjuvant trastuzumab, I favor using lapatinib, probably in combination with capecitabine (3.1), depending on what other chemotherapy the patient has received. We have some data with lapatinib and paclitaxel, in case I wanted to use that drug.

If the interval between stopping adjuvant trastuzumab and the recurrence was long, then I would seriously consider restarting trastuzumab as my first approach.

I’m interested in trials evaluating whether the two drugs in combination are better than either alone, but that is not something I’d do in a clinical setting right now.

3.1

We have a couple of other promising HER2-targeted agents in the pipeline. Pertuzumab is a fascinating drug. I’m most fascinated by T-DM1, which is trastuzumab conjugated to a maytansine derivative.

It delivers chemotherapy directly to the tumor cell. I believe that’s smart therapy, with exciting early data (Beeram 2007). Using trastuzumab for drug delivery is a fascinating approach.

Track 7

Arrow DR LOVE: Can you describe your experience with lapatinib?

Arrow DR GRALOW: I’m using it, and I’m certainly seeing beneficial effects. We’re still in the phase of integrating it into practice. Capecitabine/lapatinib can be complicated to administer.

It’s a completely oral regimen with many pills. Capecitabine is taken twice a day for only two out of three weeks. Lapatinib is taken once a day. One drug is taken before eating anything, and the other is taken later.

So it’s complicated, and we spend a lot of time teaching, reinforcing and making phone calls to make sure patients haven’t mixed up the drugs. It has involved a learning curve.

The nurses need to know what must be reinforced, and we need to know how to counsel patients better. We have some great teaching materials now. I’ve seen efficacy with lapatinib, but also rash and diarrhea. It’s a regimen we’re still getting comfortable using.

Arrow DR LOVE: What have you seen in terms of rash?

Arrow DR GRALOW: Facial and truncal rash. My group treats only patients with breast cancer, so we don’t have much experience with EGFR-targeted therapy. Many practicing oncologists have already learned how to deal with that, but our group has not had much experience.

We’ve learned of some topical treatments that we can use. We don’t usually use oral antibiotics, but we have done so. We’re getting better at managing the rash.

From the patients’ standpoint, the rash is visible. They can tolerate it on their chest if they can cover it. When it’s on their face, however, they don’t like to be labeled or have people ask about it.

Track 8

Arrow DR LOVE: Can you talk about brain metastases in patients with HER2-positive breast cancer and where lapatinib might fit in?

Arrow DR GRALOW: We’re clearly seeing more brain metastases as first or dominant sites of recurrence in patients with HER2-positive disease. Is it related to the biology of the HER2 tumor cell? My perspective is that we’re controlling all the other sites of disease better.

Patients aren’t dying as quickly of liver disease, and they’re living long enough to manifest the symptoms of their brain metastases, another common site of recurrence.

It’s partly biology and partly that we’re doing better at controlling the disease in the rest of the body.

Trastuzumab is a large monoclonal antibody that shouldn’t be able to cross the intact blood-brain barrier. Some anecdotal case reports, however, indicate that once you have a large metastasis that disrupts the blood-brain barrier, you can obtain tumor shrinkage with trastuzumab.

Lapatinib certainly penetrates the blood-brain barrier, and we have, again, some anecdotal evidence suggesting that we can achieve tumor shrinkage with lapatinib alone. Nancy Lin and the group at Dana Farber have conducted some elegant studies for patients with HER2-positive brain metastases who received radiation therapy and whose disease was progressing. They added lapatinib as a single agent, and then at progression or with no response, they added capecitabine (Lin 2007).

Using conventional measures, lapatinib alone has not produced much of a response. It’s making a dent, but it doesn’t meet the classic response criteria.

When patients on those studies experienced disease progression or no response on lapatinib, the next step was adding capecitabine, and quite a few responses then met conventional criteria (Lin 2007). Whether it was the combination of capecitabine/lapatinib or capecitabine alone, I’m not sure.

I’m also tantalized by evidence in the Phase III capecitabine/lapatinib versus capecitabine-alone trial, which indicated a numerical trend toward fewer brain metastases with lapatinib (Geyer 2006).

Will that translate in the adjuvant setting to a real difference that can improve survival? I don’t know. We will certainly be paying attention to that in the recently opened, international ALTTO trial for patients with HER2-positive disease.

Track 9

Arrow DR LOVE: Would you describe the design of the ALTTO trial?

Arrow DR GRALOW: ALTTO is a huge, international undertaking between the Breast International Group and the North American Breast Intergroup.

The backbone chemotherapy can vary depending on where you live. In the US, we will predominately use an anthracycline and then weekly paclitaxel, with four different ways of administering the HER2-targeted therapy: trastuzumab alone, lapatinib alone, both agents together or a sequence of the two agents with a washout period (3.2).

3.2

Everyone receives one year of the HER2-targeted therapy. We will carefully examine the efficacy and toxicity with respect to the heart.

Arrow DR LOVE: It is interesting that one of the arms does not include trastuzumab.

Arrow DR GRALOW: Much debate goes on about that arm and whether it is ethical. It’s standard in this country to use trastuzumab in that setting: Are we omitting an effective therapy in favor of an as-yet unproven therapy? In the metastatic setting, the data with lapatinib are impressive. I’ve been increasingly reassured that there’s activity, especially in combination with paclitaxel, as Angelo Di Leo presented at ASCO 2007 (Di Leo 2007).

Arrow DR LOVE: Can you talk about the BETH trial that the NSABP and CIRG are running?

Arrow DR GRALOW: Another important issue is the addition of bevacizumab to chemotherapy and trastuzumab. In the metastatic setting, data for trastuzumab with bevacizumab presented by Mark Pegram and others have shown an impressive response rate for those two agents together (Pegram 2006). Some concern has arisen about cardiac toxicity with trastuzumab and bevacizumab without chemotherapy, and this will be monitored carefully in the BETH trial (3.3).

3.3

Select Publications

 

Table of Contents Top of Page

BCU Think Tank

CME Test Online

Home · Search

EDITOR'S NOTE
Bev, BETH, BEATRICE and the next big moment in oncology
research: NSABP-C-08

Neil Love, MD
- Select publication

INTERVIEWS
Daniel F Hayes, MD
- Select publications

John F Forbes, MD
- Select publications

Julie R Gralow, MD
- Select publications

John F R Robertson, MB, ChB, BSc, MD
- Select publications

Roundtable Discussion
- Select publications

Breast Cancer Update:
A CME Audio Series and Activity

Faculty Disclosures

Editor's Office

Paik Video

Media Center
PDF
Media Center
Podcast
Previous Editions
Home Terms and Conditions of Use | Privacy Policy
Copyright © 2008 Research To Practice. All Rights Reserved