SHARE a support group for women with breast and ovarian cancer testified at ODAC last month advocating revocation of approval. Advocates must keep alert all the time.

This wonder drug is saving many womens lives without the side effects and I find it disgusting that groups who claim they are advocates for stage four breast cancer patients are so politcally inclined. My wife has been on Avastin for nearly two years and her CTC markers remain at zero and with no new growth...oh and after each treatment she goes to work. While ODAC is ostensibly independent, it is in practice a creature of the FDA and the FDA's political masters in Congress. The agency appoints the rotating ODAC members, which is like a prosecutor choosing his jury. The agency's oncology leaders—led by cancer drugs chief Richard Pazdur—routinely stack the panel with people who share their dislike for industry and accelerated approval. In recent years the FDA has also tightened conflict-of-interest rules, which means that ODAC's "experts" often have no specific expertise treating the diseases that the drugs they are adjudicating are meant to treat. There was only one breast cancer oncologist on the ODAC panel. EXCERPT FROM THE ESTEEMED PANEL: Since PFS (progression free survival) is the endpoint being studied,” said Dr. Wyndham Wilson, the ODAC chair, “what we are here to judge is whether or not there is a clinically meaningful—from a patient’s point of view—[difference in] quality of life between the patients who received Avastin and those who didn’t.” The committee found any such difference impossible to ascertain, since the trials had not collected patient-reported quality-of-life data that could show an improvement in symptoms or psychological state in tandem with PFS. The AVADO trial collected a set of quality-of-life data, but only to show that the addition of bevacizumab (Avastin) did not decrease patients’ quality of life. Sponsors of future trials evaluating PFS should take this issue to heart, stated Dr. Pazdur. “Sponsors really need to pay very close attention to [measuring quality of life], build it carefully into their protocols, and approach it with the same degree of caution and resources…as one would with a primary endpoint,” he said. This panel seems to be covering the butts over decisions made two years ago. But every month a survivor lives, some new treatment may be discovered. Another breast cancer expert approached by Medscape Medical News, Gabriel Hortobagyi, MD, FACP, professor of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, who was present at the ODAC meeting, said: "This is an interesting development." "Bevacizumab is clearly active in breast cancer, and there is more experience with this agent in metastatic breast cancer than with many, if not most, other agents evaluated for the metastatic breast cancer indication," he said. In 3 separate randomized trials, adding bevacizumab to various commonly used chemotherapy regimens resulted in significantly improved overall response rate and time to progression. These beneficial effects were consistently found in all 3 trials and in all subgroups examined, he pointed out. "Anecdotally, bevacizumab combinations can produce dramatic responses in individual patients, and it is my clinical impression that responses of such quality are seldom seen with the same chemotherapy programs without bevacizumab. As a frequent user of this agent, I have also found that it is very well tolerated by the great majority of patients; in very few do I need to modify dose or schedule, and in even fewer do I need to discontinue treatment because of toxicities." However, a "puzzling observation" in all 3 studies is the total absence of a survival benefit - "the survival curves of the control and bevacizumab arms were entirely super imposable," Dr. Hortobagyi said. It is difficult to demonstrate a significant survival benefit in first-line therapy of metastatic breast cancer, because such benefit is often diluted by multiple subsequent treatments and crossover designs, he explained, but "we often see some separation of the curves, even if the difference doesn't reach statistical significance." "In the trials in question, and as you would expect simply by chance, some parts of the bevacizumab curves were slightly above and others slightly below the control-arm curves. While none of these differences (whether positive or negative) were statistically significant, the FDA reviewer elected to present them in an incredibly biased manner, where positive (but nonsignificant) survival differences were labeled 'no difference,' and negative (also nonsignificant) differences were labeled as favoring the placebo arm," Dr. Hortobagyi explained. "This either denotes ignorance of common statistical methods or an underlying agenda to place the agent in an unfavorable perspective. There were other surprising statements made by the FDA reviewer attributing certain toxicities to bevacizumab, when in fact those toxicities are well recognized as being associated with the underlying chemotherapy. For instance, bowel perforations are a well-recognized complication of taxanes, especially docetaxel; angina and myocardial infarction are reported complications of capecitabine; and congestive heart failure is a well-known complication of anthracyclines (doxorubicin and epirubicin)," he continued. "The FDA reviewer continuously referred to these complications as bevacizumab-related, creating an artificially high bevacizumab-related mortality rate in the minds of ODAC members," Dr. Hortobagyi said. He summarized the outcome of the meeting as follows: "ODAC members found the benefit of bevacizumab insufficient in view of the toxicities listed by both the sponsor and the FDA reviewer, and based on that belief, they felt that the 2 new trials failed to confirm the encouraging results of E2100, and that there was insufficient efficacy to expand or even maintain the metastatic breast cancer indication of bevacizumab." However, he added that "during the discussion, I got the strong impression that several ODAC members had a poor understanding of clinical trials and statistics (based on some of the questions that were somewhat bizarre!), and that very few had any experience using bevacizumab in the clinic. Otherwise, they would have known that the frequent toxicities reported on paper caused few symptoms and actually did not affect quality of life, and perhaps they would have seen the response and progression-free survival benefits in a different light." "I thought that the discussion brought to light some issues in the process. The sponsor complied entirely with the FDA's requests when accelerated approval was granted; however, the FDA instructions were vague, and the 'magnitude of benefit' was never defined. Despite the fact that the FDA never requested prolongation of survival, much of the discussion by ODAC members was based on this lack of survival benefit. Therefore, there was a major disconnect between the FDA and ODAC," Dr. Hortobagyi explained. "Ultimately, ODAC members acted on their understanding of the risk/benefit ratio of the drug, and recommended removal of the metastatic breast cancer indication. I think this was the wrong recommendation, although witnessing the process I can see how inadequate instruction by the FDA, unfamiliarity with the drug, and a biased presentation by the FDA reviewer led to this result," he said. "I am concerned, in part, because this recommendation might remove an important treatment option from patients with metastatic breast cancer. I am also concerned because 'clinical benefit' remains poorly defined. This precedent will set many drugs currently under development up for failure. It would be important for the FDA to clearly define expectations from sponsors and provide clear guidance to ODAC members, so that disconnects such as those observed during this discussion stop happening," Dr. Hortobagyi told Medscape Medical News. The Wall Street Journal ran an aggressive pro-Avastin editorial yesterday, and FoxNews (along w/ other outlets) has covered not only the issue itself, but the fact that there have been Congressional inquiries regarding the ODAC recommendation. We have some reason to believe that the Congressional and public interest in the issue led FDA to take considerably longer to release a final decision than was initially expected. It makes a big difference that Komen (the world's largest breast cancer organization) and some other groups have come out publicly against the recommendation. Had FDA made a decision immediately--which they were prepared to do-- none of this media attention or pressure from outside groups would have happened. This was the whole purpose of our letter-- to make a request that would be hard to deny, and hopefully allow time for a legitimate public backlash to emerge so that the FDA (and ultimately, Sec. Sebelius and the Obama Administration) would be fully aware how much public ire they will be asking for if the decision goes forward. They seemed to be caught off-guard by the huge, negative public reaction to the mammogram recommendations of the US Preventive Service Task Force last year, and HHS was forced to do considerable 'damage control' as a result. This time, they know what they're getting into. Media attention and public outrage might affect this decision. If it doesn't, it might at least stall the announcement of a corresponding national coverage decision by Medicare. Most insurers, for example, were not willing to discontinue regular mammogram coverage for women under 50 after the public outcry about the USPSTF recommendation-- even though that was the expected outcome.

If they take Avastin way from me while I am benifiting I am going to file a huge law suit......like 500 million as we all know this is insurance co's