A study published in the Journal of Clinical Oncology has reinforced evidence that Roche's Avastin is linked to heart failure in patients treated for breast cancer.

The meta-analysis of studies involving 3,784 patients found that 1.6% of women taking Avastin ((bevacizumab) went on to develop heart failure, compared to 0.4% among those not taking the drug.

The analysis also supported the view that Avastin treatment is associated with an increased risk of developing hypertension and other cardiovascular complications. Around 25%-30% of patients treated with Roche's drug developed high blood pressure whilst on therapy.

"This is the first comprehensive report to show that bevacizumab is associated with an increased risk of significant heart failure in patients with breast cancer," write the authors, led by Toni Choueiri  of the Dana-Farber Cancer Institute in Boston, USA.

The US Food and Drug Administration recently issued a proposal to withdraw breast cancer from the list of approved indications for Avastin on the strength of earlier analyses and the advice of its Oncologic Drugs Advisory Committee. Roche's Genentech unit has requested a hearing and until the process is completed, Avastin remains approved for breast cancer and the company maintains that the drug is an important treatment option. 

However, a withdrawal would have a significant impact on sales of Avastin, which is the world's top-selling cancer drug with annual turnover of around $6 billion, and an estimated 20% of that total coming from breast cancer indications.

Things are a little more complex in Europe. Last month the European Medicines Agency decided Avastin's benefits outweighed the risk in these patients, at least when combined with paclitaxel, although an advisory committee said it should no longer be used alongside two other chemotherapy drugs (docetaxel or capecitabine).

In an editorial accompanying the study, Nitin Verma and Sandra Swain of the Washington Cancer Institute in the USA point out that the five studies included in the meta-analysis followed very different protocols, did not include routine cardiac monitoring and differed greatly in the incidence of cardiovascular adverse events.

"The results of this meta-analysis should be interpreted with extreme caution," they note. "We still lack convincing evidence that bevacizumab is associated with an increased risk of significant heart failure."