Slides from a presentation at SABCS 2009 and transcribed comments from a recent interview with Adam M Brufsky, MD, PhD (12/23/09)

ADAM M BRUFSKY, MD, PhD: We know from trials in the first-line metastatic setting — ECOG-E2100, AVADO and RIBBON 1 — that the addition of bevacizumab to chemotherapy provides benefit. The idea behind RIBBON 2 was to ascertain whether the addition of bevacizumab to second-line chemotherapy was of benefit.

We evaluated four different second-line chemotherapy regimens — taxanes, specifically paclitaxel, nanoparticle albumin-bound (nab) paclitaxel or docetaxel, capecitabine, gemcitabine or vinorelbine — in a two-to-one randomization with or without bevacizumab. Chemotherapy was administered at standard dosages, with the exception of vinorelbine, in which the dose was a bit higher than the typical dose.

The bottom line for this trial is that there was a substantial progression-free survival benefit for the chemotherapy/bevacizumab combination — 7.2 months versus 5.1 months. We reported about a two-month improvement in overall survival with the combination, though this value only currently represents a bit more than 50 percent of the patient population on trial and has not yet reached statistical significance.

As far as safety goes, side effects were as expected — hypertension, proteinuria and three wound dehiscences on the trial in the bevacizumab arm — and no new toxicities were reported.

Also of note when analyzing the RIBBON 2 data is an exploratory analysis we performed of chemotherapy endpoints stratified by regimen. The addition of bevacizumab to a taxane regimen and to capecitabine provided a statistically significant benefit. The addition of bevacizumab to gemcitabine also provided a benefit — about 10 to 12 percent — though not statistically significant. The addition of bevacizumab to the vinorelbine arm of the study, however, did not provide a benefit and showed a detriment, which is bizarre.

We discussed this facet for a couple of months before the data were published, and I am not sure why that is. It was a limited analysis, with only 23 patients on the vinorelbine/placebo arm. It’s likely that many of the patients on the placebo arm were treated at other institutions. And it’s really a subset of a subset, so I’m not sure we should read too much into it.

I believe the take-home message for practicing oncologists is you can safely administer bevacizumab in the second-line setting. It’s as safe as it is in the first-line setting. You still have to watch out for the usual side effects. I think the chemotherapy/bevacizumab combination is something that will be added to the armamentarium of therapies that we utilize for second-line metastatic breast cancer.

Dr Brufsky is Associate Professor of Medicine and Associate Division Chief of Hematology/Oncology at the University of Pittsburgh, Co-Director of the Comprehensive Breast Cancer Center and Associate Director for Clinical Investigation at the University of Pittsburgh Cancer Institute in Pittsburgh, Pennsylvania.