FDA panel rejects arguments for cancer drug

An FDA advisory panel on Wednesday unanimously rejected arguments from Genentech that its controversial anti-cancer drug should continue as an approved therapy for advanced breast cancer.

In pointed comments, several members of the panel said the company had not demonstrated that Avastin could help breast cancer patients live longer, or improve their quality of life. They also pointed to significant side effects, including high blood pressure in many patients, and cases of hemorrhage and intestinal perforations. One panel member, Dr. Wyndham Wilson of the National Cancer Institute, said that given the data, prescribing Avastin to breast cancer patients would be akin to violating the physician’s oath of “first, do no harm.”

The final decision lies with FDA Commissioner Margaret Hamburg. Karen Riley, an FDA spokeswoman, said the official record will remain open for comment until July 28th, but beyond that, there is no timetable for a decision. While the vote is a blow to Genentech, and deeply disappointing to many of the patients who attended the hearing in support of Avastin, the drug’s status will remain, for now, unchanged. Whatever the commissioner decides, it will not affect the drug’s approval as a treatment for certain types of brain, lung, colon and kidney cancer.

Avastin received provisional approval as a breast cancer therapy in 2008, based on the results of a study known as E2100. Last year, the FDA's Center for Drug Evaluation and Research (CDER) recommended that approval be withdrawn, based on larger studies with less impressive results.

While approvals and withdrawals only become official with the Commissioner’s stamp, CDER’s opinion is usually the last word. In this case, Genentech filed an appeal for a new hearing.

The highly unusual hearing began on Tuesday, with more than two dozen patients telling their personal stories, to scattered applause, urging the panel to keep Avastin available. The debate is highly charged. Some patients have accused the FDA of letting Avastin’s high cost – as much as $88,000 for a year – cloud its judgment. By regulation, the agency is not permitted to consider cost when it evaluates the safety and effectiveness of any treatment.

Wednesday, Genentech officials defended their studies, saying that certain patients respond especially well and that side effects, while potentially serious, are no worse than with other breast cancer drugs. They pointed out that Avastin is an approved breast cancer therapy in Europe, and that the National Comprehensive Cancer Network – an influential coalition of cancer centers – also considers it a viable option. One senior scientist, Dr. Sandra Horning, told the panel that for many women with breast cancer, there are no better treatments available.

Horning also painted CDER officials as flip-floppers. At one point she noted a memo from February 2008 in which the head of the agency's cancer drugs division made positive comments about study results that he – and other CDER officials – had dismissed on Tuesday.

But the panel wasn’t swayed. In a series of 6-0 votes, they agreed that research shows minimal benefit from Avastin. None of the five studies presented showed patients on the drug actually living longer. “We can only ask patients to take on this risk [of side effects] when there is significant benefit,” said Natalie Compagni-Portis, the “patient representative” on the panel. The demonstrated improvement – on an average, several weeks before the tumor got worse – was not enough.

“This is an emotional issue," Portis said in explaining her vote. “Any amount of extra time is meaningful for patients. After E2100 there were many reasons to be hopeful. I think we all wanted Avastin to succeed. The reality is these studies we’re hearing about did not confirm that. These studies did not bear out this hope.”

The panel also rejected a request from Genentech to maintain the drug’s approval while further studies are done, to identify which patients might be “super-responders” or more susceptible to side effects.

In a statement after the vote, Genentech spokeswoman Charlotte Arnold said, “We are very disappointed by the committee’s recommendation and hope the Commissioner does not decide to remove an important medicine for women with this incurable disease who already have too few treatment options. We remain ready to collaborate with the FDA to find a solution that is in the best interest of patients who need Avastin.”