Presented at FDA Meeting on Abraxane in the Adjuvant Setting, September 6, 2006 Good morning, my name is Helen Schiff. I am speaking today on behalf of The Center for Medical Consumers. I am a breast cancer survivor and an advocate. I have no conflicts of interest to report, and have paid for my own travel expenses. Before I begin, I would like to point out a problem associated with releasing the briefing documents only 24 hours in advance of an ODAC meeting. This is really too short a period of time for most advocacy organizations to prepare a presentation. Organizations, such as SHARE in New York City, which is a breast and ovarian cancer advocacy and support organization, of which I am a member, need more than 24-hours notice to develop a position that represents the views of its membership. I suspect that the roster of consumer advocates prepared to address this and other advisory committee meetings would be much longer, and the quality of the testimony better if the briefing papers were released earlier. Even given the short amount of time and the fact that I had to get up at 4 am in the morning to be here in time, I felt compelled to weigh in on this precedent setting decision. As an advocate, I try to hold positions that are in the best interest of all women with breast cancer, not just what is best for ME or someone I know. We are concerned not only with what is best for those who have breast cancer today, but also for those thousands who will be diagnosed with breast cancer in the future. Looking at it from that perspective there is no doubt in my mind, that it would be a mistake to approve Abraxane for use in the adjuvant setting without testing this drug for efficacy and safety in this setting, in comparison with Taxol. And I think this should be the general rule for all old drugs that are delivered in new ways. Why do I think this? The most important reason is that advocates want treatments based on evidence. We also want new treatments fast. But we don’t want shortcuts that might compromise the evidence. We have had too many bad experiences with trusting what APPEARS to make sense. HDC is such an example. Another one is the CALGB trial that Dr. Hudis mentioned in his presentation today. Yes, it showed a benefit for taxol added to AC but there was no benefit from the high dose of Adria vs. the medium dose. The FDA is mandated to approve drugs that are at least not inferior to the standard of care, and as I am sure you understand, advocates really only get excited about drugs that show an actual clinical benefit—the larger the better. All you have to do is look at Doxil and Xeloda to see that changing the way a drug is delivered can make an important difference in both its efficacy and its toxicities. Doxil is doxorubicin, better known as Adriamycin. encapsulated in a pegylated liposome. The pegylation tends to keep the drug stuck in the tumor and out of the circulation. Xeloda, is 5FU formulated in a pill form instead of being given as an infusion and it is metabolized mainly at the tumor site. Both have very different side-effect profiles than the original chemotherapies upon which they are based. And we know from the comparative metastatic trial that the toxicities of Abraxane and Taxol are not the same. While Taxol caused more neutropenia and hypersensitivity reactions, Abraxane caused more peripheral neuropathy, nausea, vomiting, diarrhea, and fatigue and weakness. Of course Abraxane does not require premedication which avoids a not insignifcant toxicity that can be caused by it. It’s important for patients with primary breast cancer who are weighing the risks and benefits to have trial results in populations of patients like themselves so that they can make informed choices about treatment. There may be other, as yet unknown issues regarding efficacy, that have not emerged be cause Abraxane has been studied in so few women. For example, although Doxil is much less cardio-toxic than doxorubicin, there has been concern about out what the interaction will be when it is used in combination with other drugs in the adjuvant setting. Clearly, this kind of concern would need to be investigated in a clinical trial prior to its approval as an adjuvant treatment. Abraxane like Doxil was only used as a single agent in the metastatic setting. It is not known how it will work in combination with other drugs that would be used with it, in the adjuvants setting. . We want to make sure that inferior drugs don’t start creeping into the standard of care. We want to make sure that newly diagnosed women have the very best shot at preventing a recurrence, and of NOT dying of breast cancer. It is important to remember that therapy in the adjuvant setting is curative for some women. We want to increase the number who survive not decrease them. The stakes are very high. Once a drug becomes standard of care, it can be used as the comparator arm in a registration trial. This is an advocate’s worst fear. If the drug in the comparator arm is inferior you can end up replacing one inferior drug with another inferior drug. Advocates also try to ascertain how certain policy decisions impact the future of drug development. A decision to allow reformulated drugs with different delivery systems to skip adjuvant trials encourages the pharmaceutical industry to shift investments from developing more novel agents to developing different delivery systems for ALREADY EXISTING chemotherapy drugs. It is easier and much cheaper to do and they will come to market much faster. I am afraid that being able to secure new indications without conducting trials in large adjuvant markets would create an irresistible incentive for industry, while making the risky pursuit of novel agents even more problematic than it already is. In addition to these general considerations, I think it is important to be aware of just how weak the Abraxane data is in the metastatic setting. No time-to-progression or overall survival benefit has been established. All we see is the doubling of tumor shrinkage. And tumor shrinkage has not been proven to correlate with time to progression or overall survival in the adjuvant setting. I want to conclude by putting on my patient hat. What if Abraxane is approved for adjuvant treatment without any further trials? And let’s say I have just been diagnosed with stage 11 breast cancer. I am eager to hear what my oncologist recommends. Much to my surprise he offers me a choice Adriamycin and Cytoxan with Taxol or Adriamycin and Cytoxan with Abraxane. So naturally I ask him “Which drug will give me the greatest assurance that the cancer wil not return?” His answer: “ CURRENTLY, WE DON’T KNOW.” Taxanes will probably be in use for a long time to come. “ Will doctors always have to say: “We don’t know” ? And will they have to say “we don’t know” to all the newly formulated drugs that come on the market. I certainly hope not. Posted 9/06 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.