FDA Panel Says No to Avastin for Advanced Breast Cancer

WEDNESDAY Dec. 5, 2007 -- A U.S. Food and Drug Administration advisory panel recommended Wednesday that the cancer drug Avastin should not be used to treat women with advanced breast cancer.

In a close vote, 5-4, the advisers decided the drug's ability to slow down the growth of tumors did not outweigh the increased risk of blood clots and other cardiovascular troubles among users, the Associated Press reported. In rare cases, patients taking Avastin with standard chemotherapy have died.

Avastin was approved to treat colon cancer in 2004, and lung cancer in 2006. It works by cutting off the tumor's blood supply.

"Everybody wants to offer metastic breast cancer patients hope, but we shouldn't offer them false hope," panel member Natalie Compagni-Portis, a patient representative with Breast Cancer Action in San Francisco, said during the meeting, according to the AP. "We have to raise the bar in terms of safety."

"These patients are terminal, and it's our job to make their lives better, not to say that it's OK to have a stroke or that it's manageable," Maha Hussain, an oncologist at the University of Michigan and the advisory panel's chairwoman, said during the meeting. "You didn't show that patients are living better or that they're living longer."

In trial results submitted to the FDA by the drug's U.S. maker, Genentech Inc., use of Avastin (bevacizumab) did boost the progression-free survival of women with advanced breast cancer by an average of 5.5 months, when combined with the chemotherapy drug paclitaxel. Progression-free survival refers to survival without any advancement of the malignancy.

However, the same Genentech study of 722 patients showed that patients reaped no gain in terms of their overall survival after taking Avastin.

Another company-funded trial, this time including 462 patients with advanced breast cancer, showed similar results, with Avastin having no effect on overall survival.

At the same time, the FDA said, the drug has "major safety issues," including hypertension, clotting events, left ventricular heart dysfunction, heart attack, gastrointestinal perforation and proteinuria (excess protein in urine). A special FDA staff review of the data found that rates of grades 3 to 5 toxicities rose by more than 20 percent when cancer patients received Avastin on top of regular chemotherapy.

Furthermore, in the Avastin-paclitaxel trial, the rate of patient deaths linked to Avastin use was 1.7 percent (six out of 363 users) compared to no deaths among the 348 participants who did not receive the drug, the FDA noted.

In its approval submission statement to the FDA, Genentech contended that, "Analysis of the safety and efficacy data in total demonstrates a highly favorable risk-benefit profile for bevacizumab in combination with paclitaxel that supports full approval of bevacizumab for the treatment of locally recurrent and metastatic breast cancer."

The FDA is not obligated to follow the recommendations of its advisory panels, but usually does. A decision is expected by Feb. 23, the AP reported.

Avastin is not traditional chemotherapy, but instead is a monoclonal antibody that robs tumors of their blood supply. It has been found to boost the survival of patients with metastatic colorectal cancer and non-small-cell lung cancer when added to chemotherapy and used as a first-line treatment.

But the drug has its downside. In an analysis of pooled data from five randomized controlled trials involving more than 1,700 patients with metastatic colon, breast or lung cancers, Genetech researchers found that 3.8 percent of patients experienced blood clots while on the drug, compared to 1.7 percent of those who took standard chemotherapy alone.

Patients who were 65 or older appeared to be at special risk for clots while taking Avastin, according to the study, which was published in August in the Journal of the National Cancer Institute.

The exact link between Avastin and cardiovascular risk remains unclear, although the Genentech team speculated that a vascular endothelial growth factor (VEGF), a natural compound that boosts blood vessel growth, may play a role.

Posted: December 2007


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