Avastin Gets Surprise Breast Cancer Boost From FDA

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Main Category: Breast Cancer
Also Included In: Regulatory Affairs / Drug Approvals;  Cancer / Oncology;  Women's Health / Gynecology
Article Date: 24 Feb 2008 - 6:00 PDT

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Genentech's Avastin, a drug which is currently used to treat colon and lung cancer, has been approved by the FDA for breast cancer treatment. Earning approximately $2.3 billion in the USA alone in 2007, this new approval is expected to boost Avastin sales by at least $500 million. Experts had expected the Food and Drug Administration (FDA) to either delay or turn down Genentech's breast cancer application after an Advisory Panel narrowly recommended rejecting breast cancer treatment with Avastin last December.

New positive data was published recently - A Phase III study(E2100) that showed that Avastin in combination with paclitaxel chemotherapy resulted in a 52% reduction in the risk of disease progression or death compared to patients treated with paclitaxel alone and a doubling in progression-free survival (PFS) (based on a hazard ratio of 0.48; p<0.0001).

Roche Holding AG, which is a major holder of Genentech stocks, markets Avastin worldwide outside the USA.

The FDA accelerated approval is for Avastin (bevacizumab), in combination with paclitaxel chemotherapy, for the treatment of patients who have not received chemotherapy for their metastatic HER2-negative breast cancer. Accelerated approval means the FDA approves products for life-threatening diseases based on initial positive clinical data.

Genentech says that it has "shared with the FDA a summary of the results from a second positive Phase III trial (AVADO), and is expecting results from a third Phase III trial (RIBBON I) in first-line metastatic breast cancer in late 2008. A full review of both the AVADO and RIBBON I data by the FDA will be required for the accelerated approval to be converted into a full approval." Data from three randomized trials that are either planned or ongoing will be submitted to the FDA, the company informs.

In a Genentech news release, Kathy Miller, M.D., Associate Professor of Medical Oncology, Indiana University School of Medicine, Head Researcher on the E2100 trial, said "There is no cure for metastatic breast cancer so it is important to control the disease as early and for as long as possible. Now with Avastin plus paclitaxel, we can increase the time a woman's cancer is kept under control, and offer a biologic option to women who previously were limited to chemotherapies alone."

Breast cancer is the second most common cancer for women in the USA; it is the biggest cancer killer of women in the country. Approximately 178,000 women were diagnosed with breast cancer in the United States in 2007. About 40,000 American women died of breast cancer in 2007 (American Cancer Society).

E2100 Trial

E2100 was a multicenter, randomized and controlled clinical trial involving 722 women with previously untreated, locally recurrent or metastatic breast cancer. The women were randomized to receive weekly treatment with paclitaxel every 3 out of 4 weeks, with or without Avastin. Based on an independent, blinded review of patient scans, those treated with Avastin plus paclitaxel experienced median PFS was 11.3 months versus 5.8 months in the paclitaxel alone arm. The independent review showed a similar significance of benefit relative to the initial results presented by the Eastern Cooperative Oncology Group (ECOG) at the American Society of Clinical Oncology annual meeting in 2005. A secondary endpoint of overall survival was 1.7 months longer in the Avastin-containing arm (with a hazard ratio of 0.87), supporting the primary endpoint of PFS. This improvement did not reach statistical significance (p=0.14).

Grade 3/4 adverse events that occurred more often in the Avastin arm included neuropathy (due to longer time on paclitaxel treatment), high blood pressure (hypertension), arterial thromboembolic events and proteinuria. These safety findings were in general consistent with earlier Avastin plus chemotherapy trials and no new safety signals related to Avastin were observed.

Avastin Safety

Avastin has a well-characterized safety profile in its approved indications. The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common severe adverse reactions (NCI-CTC Grade 3-5) across clinical trials in mCRC, NSCLC, and mBC that occurred at a higher incidence (greater than or equal to 2 percent higher rate v. controls) were hypertension, proteinuria, and headache.

www.avastin.com.

Written by - Christian Nordqvist


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