A randomized trial found bevacizumab (Avastin) failed to improve outcomes in combination with chemotherapy in early triple-negative breast cancer, adding to the string of failures for the drug.

Invasive disease-free survival (DFS) and preliminary overall survival (OS) results showed no significant advantage to the addition of bevacizumab compared with adjuvant chemotherapy alone, David Cameron, MD, of Edinburgh University in Scotland, and colleagues reported in the BEATRICE trial.

But there was some good news: The researchers found outcomes were somewhat better than the literature would suggest for this group of patients not responsive to estrogen-, progesterone-, or HER2-targeted agents, with 83% to 84% without invasive cancer recurrence at 3 years.

“But in terms of improvement in outcomes, giving 1 year of bevacizumab isn’t the answer,” he said at a San Antonio Breast Cancer Symposium (SABCS) press conference.

The findings followed on the heels of negative results at the same meeting from the LEA trial suggesting no benefit to bevacizumab as an add-on to hormonal therapy in advanced breast cancer.

The drug lost its approval for use in breast cancer late last year, after studies required by the FDA as a condition of its fast-track indication in metastatic HER2-negative breast cancer failed to confirm even much of a progression-free survival advantage.

“It’s getting to the point where it’s going to be difficult to know the role of bevacizumab, if any, in breast cancer,” commented C. Kent Osborne, MD, of Baylor College of Medicine in Houston, who moderated the SABCS press conference.

“If it’s going to work, you would think it would work in this situation,” he explained. “What we’re dealing with at that stage are microscopic metastases that haven’t developed a sufficient blood supply yet. If you can prevent that blood supply from forming, you might have a more dramatic effect than in already established tumor like in metastatic breast cancer.”

Osborne called the BEATRICE results disappointing and suggested a limited role for the drug unless other ongoing studies show otherwise.

The trial included 2,591 women with centrally confirmed triple-negative invasive early breast cancer starting adjuvant chemotherapy with a taxane or anthracycline or both.

The women were randomized to four to eight cycles of the physicians’ choice of those cytotoxics either alone or with the addition of 5 mg/kg per week bevacizumab, which was continued afterward for a total of 1 year of treatment.

For the primary endpoint, invasive DFS rates were 83.7% with bevacizumab compared with 82.7% in the control group, for a hazard ratio of 0.87 (P=0.181). Invasive DFS was selected as the primary endpoint, “just as a check to make sure we’re not inducing cancers in other areas,” Cameron explained.

Interim OS results, with only 59% of the planned number of events accrued, suggested a similar hazard ratio of 0.84 for bevacizumab compared with chemotherapy alone (P=0.232).

An adequately-powered comparison of survival is expected in about a year, Cameron noted, though he said the results at least clearly show no evidence of harm.

Toxicity followed the known profile of the drugs. The analysis paid particular attention to cardiovascular risks, which Cameron noted have been of particular concern with bevacizumab, similar to trastuzumab (Herceptin).

A prospectively-measured ejection fraction drop of at least 10% to fall under the entry criteria threshold of 50% was more common in the bevacizumab group. NYHA class III or IV heart failure occurred in 0.5% and 0.6% of patients, respectively, without any cases in the chemotherapy alone group.

But about 80% of clinically-significant heart failure cases recovered.

“Yes, there are changes in ejection fraction, there is a low rate of more severe heart failure, but this is not outside of what we would have expected with this drug,” Cameron concluded.

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Primary source: San Antonio Breast Cancer Symposium
Source reference: Cameron D, et al “Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer” SABCS 2012; Abstract S6-5.