Overall consensus of agency and CDER was that drug’s benefits do not outweigh the risks.

Genentech’s last hope for retaining the metastatic breast cancer (MBC) indication of Avastin rests with FDA Commissioner Margaret A. Hamburg, M.D., after an advisory panel on Wednesday unanimously recommended reversing the agency’s approval of the $7.7 billion drug for the disease.

In a trio of 6–0 votes, the Oncology Drug Advisory Committee (ODAC) sided with agency staff officials, who concluded that Avastin does not prolong overall survival in patients with breast cancer or offer a benefit in slowing the progression of the disease that outweighs the drug’s risks.

Commissioner Hamburg, however, has final say on whether the FDA will ultimately side with or overrule ODAC. Until then, FDA’s 2008 approval remains on the use of Avastin with the chemo drug paclitaxel for women with HER2-negative metastatic breast cancer. The agency will accept public comment through July 28—a two-week extension of the original July 14 deadline, extended at the request of Genentech, a unit of Roche.

“There was some hope that perhaps there was a subset of patients that responded favorably, and it seems that that’s not the case,” said Natalie Compagni-Portis, Psy.D., ODAC’s lone patient representative, according to a hearing transcript furnished in real time by the FDA. “I also was concerned that the likelihood of this study being actually enrolled in a timely way would be compromised, which means that women would continue to be subjected to an unproven treatment with known serious risks, the risk of death, and no guarantee of increased survival or an improved quality of life.”

Hal Barron, M.D., Genentech’s chief medical officer and head of global product development, said in a statement that the company was “very disappointed” by ODAC’s recommendation, and hoped that Commissioner Hamburg would overrule the panel and retain Avastin with paclitaxel for MBC.

“We remain ready to collaborate with the FDA to find a solution that is in the best interest of patients who need Avastin,” Dr. Barron said.

During a two-day hearing that ended Wednesday, Genentech proposed conducting a new clinical study examining the effect on MBC of Avastin with paclitaxel, compared to paclitaxel alone in patients who have not received chemotherapy for metastatic Her2-negative breast cancer. It would also assess VEGF-A, which has been found to be a biomarker for patients more likely to benefit from the treatment.

ODAC panelists and FDA staffers expressed doubt that a new study would show much better results than earlier studies. One of those studies (E2100) showed a 5.5-month increase in progression free survival (PFS) from 5.8 to 11.3 months, based up on which FDA conditionally approved the MBC indication for Avastin in 2008.

Last year, however, FDA began efforts to withdraw the MBC indication in line with a Center for Drug Evaluation and Research recommendation after other clinical studies combining Avastin with other chemo drugs failed to replicate or surpass the duration of PFS seen in E2100. Genentech said the later studies still showed some PFS benefit linked to Avastin use, and that the initial 5.5-month PFS was the largest in median PFS observed in a first-line MBC trial.

Genentech and the FDA clashed over what the primary endpoint of clinical studies should be: PFS, as the drug developer is seeking, or overall survival, as the agency wants.

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