Continuing Bevacizumab at Progression

DR CARLSON: In the clinical setting, I’m not continuing bevacizumab for patients with progression of disease while on a bevacizumab-containing regimen. We don’t know the answer about the optimal duration of bevacizumab and whether we would obtain continued, repeated synergy with bevacizumab.

The typical practice pattern, at least on the West Coast, is to continue trastuzumab after progression, but I believe the general pattern is not to continue bevacizumab after progression. I hope we learned from the trastuzumab experience and will quickly initiate clinical trials to help us definitively answer the duration question with bevacizumab.

Breast Cancer Update — Think Tank Issue 1, 2007

DR MATTHEW J ELLIS: If ECOG-E2100 does not show an overall survival advantage, then bevacizumab is another palliative drug for the treatment of metastatic breast cancer with the potential to relieve symptoms.

If that were the case, I would not use bevacizumab for asymptomatic patients because they have no symptoms to palliate. I would probably reserve it for patients who are heavily symptomatic with visceral crisis, for whom response is critical. If bevacizumab improves survival, my view will change.

DR BUZDAR: Let’s say that no survival advantage is demonstrated. Still, in metastatic disease, the idea is to control the disease for as long as possible. If you start with a combination therapy of biologics and chemotherapy and you control the disease in a much higher number of patients for a much longer period, that is a major achievement from the patient perspective, even though long-term survival may not be affected.

Breast Cancer Update 2007 (3)

DR WINER: I struggle with what to do with patients who received adjuvant taxanes less than a year ago and then experienced recurrence. Fortunately, it doesn’t come up too often. Those types of patients were excluded from ECOG-E2100. About 20 percent of the patients in ECOG-E2100 had received a prior taxane but not in the past year.

I am unenthusiastic about using a taxane again for that patient, so that would be a setting in which I would still want to use bevacizumab. I would use it either with capecitabine or vinorelbine. We conducted a Phase II trial with vinorelbine demonstrating that it was safe and reasonably effective, but I still don’t believe we know what to do with these patients.

Breast Cancer Update 2007 (2)

DR SEIDMAN: Currently, I generally follow the ECOG-E2100 paradigm. For patients who are not participating in our AC/nab paclitaxel/bevacizumab pilot trial but for whom taxanes are appropriate, I use paclitaxel and bevacizumab. Occasionally, I will have patients who have received an adjuvant taxane within the past year and have relapsed, and my inclination at that point is to use capecitabine and bevacizumab, based on Kathy Miller’s reported Phase III trial. Those are probably the two most common scenarios.

Despite the doubling of the response rate, it does concern me that the trial of capecitabine and bevacizumab did not show a significant increase in the time to progression. Certainly a difference is evident between that population and that of the E2100 trial with regard to the extent of prior therapy.

I don’t see any reason to suspect that the addition of bevacizumab to one particular cytotoxic agent in breast cancer versus another will make a big difference in terms of efficacy. The RIBBON 1 trial, which allows a repertoire of commonly used chemotherapy regimens in the first-line setting, should inform us whether we need to worry about which agent we combine with bevacizumab.

Breast Cancer Update 2007 (1)

DR HYMAN B MUSS: Before the paclitaxel/bevacizumab trial, I would have used capecitabine as first-line treatment for most patients. The truth is, whether you’re 25 years old with metastatic breast cancer or 85 years old, it’s palliative therapy.

For someone who’s been through adjuvant therapy, who has incurable disease and who is getting used to the fact that she has a serious problem, using a drug that doesn’t cause hair loss, doesn’t usually cause myelosuppression and allows her to maintain a pretty good quality of life — when she’s just been hit with the terrible news that she has an incurable metastatic breast cancer — seems like a good way to take care of a patient. The bevacizumab data are intriguing, but I still believe, for many patients, capecitabine has a potential role up front.

Breast Cancer Update 2006 (7)

DR TRIPATHY: I have tried to practice the way the ECOG-E2100 trial was designed, using bevacizumab for patients only as first-line therapy. I use it with paclitaxel, and I tend to reserve it either for patients who are symptomatic or for those who may not be symptomatic but whose disease trajectory is such that I would predict they might become symptomatic soon. It’s a judgment call.

In terms of whether or not we might want to generalize this and combine bevacizumab with other chemotherapeutic drugs, I believe that’s a reasonable consideration. For patients who have already received a taxane in the adjuvant setting, should we use a drug like capecitabine? I believe it would be reasonable.

Progression-Free Survival Benefit

DR CARLSON: The prolongation in progression-free survival that was required by both the clinical investigators and the community oncologists in these responses astounded me. I find a four- to five-month prolongation in progression-free survival as a requirement to adopt a new therapy an enormous advantage.

I would be happy with a much smaller progression-free survival advantage. I believe a four- to five-month difference would be nationally practice changing overnight. One- to two-month changes are still significant enough to probably shade my choices in the clinic.

Four- to five-month differences between therapies for metastatic disease are enormous differences. We’ll argue in many clinical trials about a few percentage-point differences in five-year survival or even disease-free survival, or a month or two difference in prolongation of survival.

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