Breast Cancer Update — Think Tank Issue 1, 2007

DR MARK D PEGRAM: I was impressed by the ECOG-E2100 data. The hazard ratio is reminiscent of our experience in the pivotal trial of trastuzumab as first-line therapy for HER2-positive metastatic disease. Moreover, if you look at the one-year survival outcome differences, you see that they also fall right on top of the one-year survival differences that were recorded early on in the trastuzumab pivotal trial.

Clearly we have demonstration of efficacy in terms of improved time to tumor progression. The overall survival data are not yet mature for that data set, but I would expect they should be this year. The last time Kathy Miller updated that data set, I believe only about 30 percent of the final number of survival events had occurred. So we’ll have to wait for the final analysis.

The question of bevacizumab as second-line therapy is being addressed in the ongoing RIBBON 2 study. Patients on that study are able to select from a menu of different chemotherapy options at the investigator’s discretion, and then they are randomly assigned to bevacizumab or placebo in the second-line setting. Short of any data from such a trial, I probably would not routinely recommend bevacizumab in a second-line setting because we have literally no data to support it at this time.

DR BRIAN LEYLAND-JONES: In terms of activity in the second-line setting, Mark is absolutely right. We have no data, but I have the feeling we will be seeing significant activity with bevacizumab in the second- and third-line settings for metastatic disease.

DR WINER: I don’t believe you can think of this as another combination therapy like a taxane with capecitabine or gemcitabine. It’s important to recognize that a previous randomized trial of bevacizumab with capecitabine in the second-line setting was largely negative, although a hint of activity was evident.

I don’t believe we should be too rigid about defining first- and second-line therapy because so much of this depends on what someone has received in the adjuvant setting. A woman who received adjuvant TAC or AC paclitaxel nine months ago and now has a relapse is technically in the first-line setting and is far more refractory than many who are in the second-line setting who might not have received adjuvant chemotherapy.

So for the woman who received adjuvant AC a few years ago and capecitabine as her first-line regimen, I’m willing to try paclitaxel and bevacizumab, recognizing that ECOG-E2100 limited eligibility to patients who had not received chemotherapy in the metastatic setting.

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DR BUZDAR: The E2100 data clearly demonstrated that inclusion of a biologic with paclitaxel substantially improved the response rate and time to progression. This is a viable positive lead, and we need to discuss it with every patient who meets those eligibility criteria. The next generation of trials will answer more clearly whether in the second- and third-line settings the inclusion of bevacizumab will enhance the response rate.

Breast Cancer Update 2006 (6)

DR BURSTEIN: We evaluated a program of low-dose, oral, “metronomic chemotherapy,” which consists of 2.5 milligrams of methotrexate twice daily for two days each week with 50 milligrams of daily, oral cyclophosphamide with or without the addition of bevacizumab in a small, randomized Phase II trial. We saw modest activity with the metronomic chemotherapy — approximately a 10 percent response rate. We also saw a somewhat greater response rate — 30 percent — and a modest improvement in time to progression — from two months to 5.5 months — with the addition of bevacizumab.

This remains an investigational and innovative approach. For patients with slow, indolent breast cancer, it may be an option to consider. For patients with the virulent form of breast cancer, that is not an approach I would attempt.

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