A clinical trial on Avastin (bevacizumab), a cancer drug that is already approved in the US as a treatment for colorectal and lung cancers, showed that the drug, when used in combination with chemotherapy in patients with advanced breast cancer, helped them to live longer without their disease advancing.

Makers of Avastin, California-based Genentech Inc, who are owned by Roche, the sponsors of the AVADO Phase III trial, said in a prepared statement that their drug had “met its primary endpoint of prolonging progression-free survival (PFS) in patients who had not received prior chemotherapy for their locally recurrent or metastatic HER2-negative breast cancer.”

The AVADO study compared the effect of Avastin combined with docetaxel chemotherapy against a placebo with the same chemotherapy. Two doses of Avastin were tested: 15 mg/kg or 7.5 mg/kg every three weeks.

The results showed that both doses of Avastin combined with chemotherapy showed statistically significant improvement in how long patients lived without disease progression compared to the placebo and chemotherapy arm.

The company said the trials showed no new safety issues.

Later this month, on 23rd February, the US Food and Drug Administration (FDA) is expected to reveal its decision on whether to license Avastin, for use in combination with another chemotherapy drug, paclitaxel, in treating patients with locally recurrent or metastatic HER2-negative breast cancer and who have not had chemotherapy before.

Senior vice president, Development and chief medical officer at the company, Dr Hal Barron said they were pleased that the the second Phase III study was successful in prolonging progression free survival (PFS) and that the trial also showed the drug’s potential with a different chemotherapy. He added that:

“The AVADO data are not included in the supplemental Biologics License Application currently under review by the FDA. However, we have shared the AVADO data with the FDA to assist the agency in assessing the risk and benefit of Avastin in this patient population.”

In December last year, an FDA advisory panel voted against granting a license for Avastin with advanced breast cancer patients because there was not enough data to show a favourable risk/benefit analysis in this setting, but the company said they believe this latest set of results will address that.

According to the New York Times, the FDA and the advisory panel were also concerned that the previous data did not clarify precisely when the cancer started to progress or get worse. Also, the initial clinical trial on the drug was carried out without some of the procedures the FDA likes to see. The latest trial is said to have these in place, said the paper.

Breast cancer is the second leading cause of cancer deaths among women in the US, and is the second most common cancer. The American Cancer Society estimates that 178,000 American women were diagnosed with the disease, and 40,000 died from it in 2007.

According to figures from Genentech, about 75 per cent of women with newly diagnosed metastatic breast cancer (where the cancer has spread to other parts of the body), have the HER2-negative type that is targeted by Avastin.

Avastin was the first drug of its kind to be approved by the FDA for use with chemotherapy to treat metastatic colorectal cancer and advanced, non-squamous, non-small cell lung cancer. Avastin is an anti-angiogenesis antibody that stops the generation and maintenance of blood vessels that feed tumours. It does this by inhibiting the production of vascular endothelial growth factor (VEGF), a protein that is important in angiogenesis.

The drug is currently being studied in more than 300 clinical trials on more than 20 different types of tumour.

AVADO was a randomized placebo controlled trial, carried out at several centers throughout the world with a total of 736 participants who had not yet been treated for locally recurrent or metastatic HER2-negative breast cancer. Patients were in three groups, one took 15 mg/kg of Avastin, another took 7.5 mg/kg of Avastin, and the third took placebo. All groups were also treated in combination with docetaxel at 100 mg/m2 every three weeks and underwent nine cycles altogether. The primary end point was PFS.

Avastin was first approved by the FDA in February 2004, as a first line drug for treating metastatic colorectal cancer with intravenous 5-FU-based chemotherapy. The drug is also indicated as a second line treatment for patients for with metastatic carcinoma of the colon or rectum. The drug was approved by the FDA in 2006 for use with carboplatin and paclitaxel chemotherapy as a first-line treatment for patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer.

According to Reuters news agency, an analyst said the new study results could “swing the balance” in favour of the FDA giving approval for Avastin as a breast cancer treatment this time around.

Click here for FDA information page Avastin (FDA).

Sources: Genentech press release, New York Times, Reuters.

Written by: Catharine Paddock, PhD