Clinical Use of Bevacizumab

DR CARLSON: I believe that some of the difference in the use of bevacizumab for breast versus colorectal cancer relates to the perception that breast cancer is a much more responsive disease. The oncologist has a much broader number of treatment options for the patient with breast cancer.

Some of the difference may also be a result of the trial of capecitabine with or without bevacizumab. While capecitabine and bevacizumab were associated with higher rates of response and longer durations of response, the trial did not meet the threshold for overall survival, which was the primary endpoint. So that study has been reported as a negative trial, although you can consider it in ways that suggest it was a positive trial.

But the fact that it was a negative trial and the trial of paclitaxel with or without bevacizumab was a positive trial — we have one trial on each side in terms of the perception of bevacizumab as an active agent — gives oncologists comfort in not using bevacizumab as first- or second-line therapy.

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I have used a fair amount of bevacizumab, almost exclusively as first-line therapy outside of any protocol. We are participating in the RIBBON 2 trial, which is evaluating the use of chemotherapy of the physician’s choice with or without bevacizumab.

That study will help us answer the question about capecitabine with or without bevacizumab and other chemotherapies with or without bevacizumab in the second-line setting.

In the first-line setting for metastatic disease, I consider a number of factors when selecting chemotherapy. How recent was the adjuvant therapy? What did the adjuvant therapy consist of? I investigate the patients’ comorbidities to understand if they have underlying neuropathy, diabetes or cardiovascular disease. I consider the patient’s age, and I consider how the woman will be able to handle an aggressive therapy.

Then I involve the patient. Typically, for a woman with newly diagnosed metastatic breast cancer who is going to receive chemotherapy, I’ll provide two or three different options, including a clinical trial if one is available.

I have not used bevacizumab with combination chemotherapy to date. The toxicity experience with bevacizumab is, for the most part, quite acceptable, but you do have to be careful. You have to monitor blood pressure, proteinuria and so forth. But the usual toxicity experience is favorable. I would expect it would be an agent you could use with combination chemotherapy without untoward toxicity.

Breast Cancer Update 2006 (4)

DR KATHY D MILLER: I would like more information about the patients with ER-positive disease who don’t yet need chemotherapy. The patients in ECOG-E2100 were receiving first-line chemotherapy for metastatic disease, but many of them had metastatic disease for several years and were treated sequentially with hormonal agents before enrolling in E2100. Estrogen increases VEGF expression, so a biologic rationale exists for combining bevacizumab with hormone-based therapies.

A safety trial is ongoing with letrozole (UCSF-037518). It’s a trial that I hope people will not interpret the wrong way and become disappointed. I’ve already heard some people say they weren’t very impressed with the response rates in the early reports.

This trial was designed purely to investigate safety. So it allowed patients who had been on an aromatase inhibitor for any period of time for metastatic disease, but whose disease was not actively progressing, to enroll and have bevacizumab added. Most of the patients reported so far had been on an aromatase inhibitor for quite some time before bevacizumab was added.

I wouldn’t expect to see these patients, who had prolonged stable disease and didn’t have easily measurable disease, to suddenly show an easily identified objective response just by adding bevacizumab. It is definitely going to take a much larger study, with bevacizumab added at the time of the initial hormonal therapy, to really see the benefits. However, this was a first step in investigating whether any unique safety issues arose from combining bevacizumab with hormone therapy. They certainly found no safety signals that would limit you from moving forward.

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