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

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