Adding bevacizumab to three different chemotherapy regimens for patients with metastatic or locally advanced breast cancer slightly increased progression-free survival but had no effect on overall survival in a manufacturer-sponsored trial. Bevacizumab was associated with a higher frequency of adverse effects.

Metastatic breast cancer is poorly treatable despite the wide range of chemotherapy regimens that have been tried against it. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, has shown some efficacy in some tumours: the aim of this trial was to examine its effects in metastatic breast cancer. Participants were women with HER2-negative metastatic or locally recurrent breast cancer not treated with chemotherapy. They were randomised to bevacizumab or placebo, plus one of three chemotherapy regimens chosen prior to randomisation (capecitabine-based, taxane-based, or anthracycline-based). Primary endpoint was progression-free survival (PFS), with overall survival a secondary endpoint; patients were evaluated every nine weeks.

In total, 1,237 patients were enrolled between December 2005 to August 2007: median follow-up was 15.6 months for the capecitabine group and 19.2 months for the others. At the end of the study, PFS was longer in the bevacizumab-containing groups. Compared to placebo, PFS increased from 5.7 to 8.6 months in the capecitabine group (hazard ratio [HR], 0.69; 95% CI, 0.56 to 0.84; log-rank P < 0.001) and from 8.0 to 9.2 months in the other two groups (HR, 0.64; 95% CI, 0.52 to 0.80; log-rank P < 0.001).

There was, however, no significant difference between bevacizumab and placebo in overall survival. In all groups, moderate to severe adverse effects were more frequent in the bevacizumab groups, and there were more drug-related discontinuations in the taxane and anthracycline-based bevacizumab groups.

The authors of the study conclude that adding bevacizumab to existing chemotherapy regimens for patients with HER2-negative metastatic breast cancer provides clinical benefit, and therefore the drug should be added to first-line treatment for such patients.

An accompanying editorial disagrees with the study authors' conclusion. The author considers that although the results from the trial (and related studies) were statistically significant, they were not clinically compelling. Benefits in PFS were smaller in the two more recent trials than in the earliest, and none showed any significant benefit on overall survival. In all trials, bevacizumab was associated with greater toxicity, and there are questions over a potential increased risk of heart failure. The author notes that in addition to the lack of survival advantage with bevacizumab, it is extremely expensive even by the standards of chemotherapy drugs. As a result, it has a very poor cost-effectiveness ratio: NICE in the UK gave an estimate for the best results with bevacizumab (combined with paclitaxel) for the first line treatment of metastatic breast cancer of £110,000 to £259,000 per QALY.