Avastin: a tale of appalling approval

I love the idea of starving a tumour to death by cutting off its blood supply. That is what anti-angiogenic drugs are supposed to do. But first, what exactly is angiogenesis? I have mentioned this process here and there but don’t think I really have dealt with it in much depth. So yesterday and then today, after getting home from work, I looked it up.

From a previous post we know that tumours cannot grow beyond a certain size (the size of a sesame seed, I read!) because of a lack of oxygen and nutrients. But, unfortunately for us, tumours are very adaptable, so instead of kicking the bucket they start secreting a horde of growth factors (e.g., the infamous VEGF, or vascular endothelial growth factor) which induce angiogenesis, or blood vessel growth. The tumour is thus able to receive a constant supply of nutrients and can grow inside of us like a nasty weed. Without the process of angiogenesis, tumours wouldn’t be able to grow or spread.

In 2004, an anti-angiogenic drug called bevacizumab (trade name: Avastin) was approved by the FDA “for use in combination with standard chemotherapy in the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer. In 2008, it was approved by the FDA for use in breast cancer, against the advice of its advisory panel.” (source: Wikipedia) Say WHAT??? Against the advice of its own advisory panel???
 
How could something so bizarre happen? I went to read the February 22 2008 New York Times article (http://tinyurl.com/yu3xx5) dealing with this subject (notice that it’s printed in the “Business” section of the paper…this will make sense as you read on…). An excerpt: “FDA approval for late-stage cancer treatments is usually contingent upon data showing a drug extended, or improved the quality of, patients’ lives. Avastin showed neither in a study, according to Genentech’s application.” NEITHER? Ehhhh?
 
Genentech, the pharmaceutical company that produces Avastin, showed that this drug “slowed tumor growth, without actually increasing life expectancy.” Contrary to what we read in this particular New York Times article, however, the FDA decision has a lot of breast cancer advocates and organizations very worried. And with good reason. Take a look at this February 16 2008 Science Daily article: http://tinyurl.com/2a33u7 Fatal seizures? Brain swelling? If you aren’t convinced yet, read this NY Times August 24 2007 article: http://tinyurl.com/yvuozf The news is sobering indeed. I wouldn’t go anywhere near Avastin.
 
Why am I suddenly interested in this drug? Well, I became concerned after reading a few Science Daily articles about it. It is also being discussed by myeloma patients right now. So today I checked to see if there were any clinical trials, and yes, there are currently seven trials testing bevacizumab on myeloma patients (relapsed and refractory…), mostly in combination with other drugs (bortezomib and so on). And there are 96 breast cancer and Avastin clinical trials. 96? Oh yes, I admit to being concerned, not for myself but for all the patients who are in clinical trials testing drugs with unknown side effects in the long run. And the short-term side effects are scary enough, as we have learned from the Science Daily articles.
 
A recent Ralph Moss report focused on the Avastin issue: http://tinyurl.com/2edftu An excerpt (but please go read the full report, it’s excellent on many MANY levels): “On Friday, Feb. 22, 2008, top administrators of the Food and Drug Administration (FDA) approved the drug Avastin for the treatment of advanced breast cancer. Avastin, which has already been approved for colon and lung cancer, is controversial because it has never been shown to extend overall survival (OS) in breast cancer patients. It has been shown to improve disease-free survival (DFS) by as much as 5.5 months, but disease-free survival is not by any means the same thing as overall survival. A patient receiving Avastin may have a 5.5 month improvement in disease-free survival yet still die at approximately the same time as someone who did not receive the drug.”

Need I mention that Genentech’s stock, which had been declining, according to a February 23 2008 New York Times article (http://tinyurl.com/26zts4), after the FDA approval…all of a sudden rose more than 8 percent? Money, profit, and more money…but who CARES about the patients??? Certainly not the CEOs whose pockets are being lined with blood money.

Ralph Moss ends his report attacking the FDA’s double standards: on the one hand, this agency is always ready to squash any promising CAM (complementary and alternative medicine) treatments, on the other, it gives a “free pass” to a big pharma company “for a drug that has yet to be proven to do anything significant for breast cancer patients.”
 
In Moss’ words, the “FDA has once again significantly lowered its standards for drug approval. If it proposed doing so across the board, including taking a more even-handed approach to CAM treatment, that would be the basis for an interesting discussion. But what FDA is doing is permitting a lower standard for the expensive products of Big Pharma, while remaining wary of all non-toxic or non-patentable agents. So, whatever happened to the level playing field that a former director of the National Institutes of Health (NIH) promised the CAM movement back in 1992? Gone with the wind.”
 
But wait, it isn’t all doom and gloom out there. Curcumin inhibits angiogenesis. No kidding. There are 85 studies in PubMed dealing with this topic. Not one. Eighty-five. I have read a few of them, myself. Oh, and so does resveratrol. But this is material for at least another post. I will leave it at that…for now.
 
Concluding thought: do we really need to strangle a tumour with drugs that are toxic, potentially fatal (some women have already died from Avastin) and outrageously expensive?

3 Comments

  1. What you say is true about clinical trials, but I did have a friend who was CURED of Hep C on one. It would be hard to sign up for one of these unless one had explored all options. Glad you are on the alternative cure though! Winnah

  2. Hi, when I look for info about conventional oncology treatments
    i read this site: http://www.oncologystat.com
    The experts on this site are happy because of avastin approval…
    see the below article

    They say it is a modest step…but it is an expensive drug
    and side effects are dangerous….and my understanding is
    that oncologists are not able to personalize treatment….
    they do not know in advance who is the patient helped
    by this drug… some are intoxicated without improvement…
    carla

    Reflections on the Long and Winding Path to Bevacizumab Approval
    2008 Feb 26, Lee Schwartzberg, MD, Editor-in-Chief

    The recent approval of bevacizumab by the Food and Drug Administration (FDA) for use with chemotherapy in women suffering from metastatic breast cancer should be viewed as a victory that stands to improve the care of thousands of women each year. The long and winding path to approval is worth some reflection. Clearly, there were issues inherent in submitting for registration a cooperative group trial not designed for that purpose. The FDA dealt with this situation by mandating a central review of imaging studies when the trial was first reviewed by the agency almost a year ago. Virtually no differences in results were obtained after this central review. An Oncology Drugs Advisory Committee (ODAC) reviewed the new data in December 2007 and voted 5-4 against approval, based on concerns about toxicity and a lack of overall survival (OS) benefit. It is telling that the clinicians on the panel with experience in treating breast cancer voted for approval, while the patient advocates and nonclinical staff voted against it.

    Yet when all was said and done, the original assumptions of the study were proven. When added to paclitaxel, bevacizumab nearly doubled the time to progression, increased the response rate, and numerically improved OS, although its effect on OS was not statistically significant. Reports recently surfaced that at least 2 members of the ODAC panel had considered changing their votes against approval to votes favoring it. On the strength of the clinical trial evidence, the FDA overruled the advice of its own panel and decided to approve bevacizumab pending the results of additional studies.

    Metastatic breast cancer remains a devastating and essentially incurable disease. Everyone wishes for an effective therapy that is inexpensive, nontoxic, and easily administered. Until that day comes, we must make value judgments about the data from clinical trials of the drugs that are developed to treat the disease now. Certain leaders of the advocacy community have taken the position that shrinking more cancers and keeping them from growing for a longer period of time is not a valuable tradeoff for patients in return for a modest increase in adverse effects. This position flies in the face of my experience as a medical oncologist treating breast cancer for more than 20 years. I believe that most practitioners would and do agree with me.

    Overall survival in this disease is obscured by the fact that most patients can respond to multiple lines of therapy, obtaining some benefit from different treatments and likely prolonging life incrementally. Trials in which additional treatment were withheld after experimental therapy would be unethical and, of course, are not pursued. Moreover, recommending against approval because of the aggregated cost of this expensive drug does a disservice to patients. Physicians make treatment decisions based on the good they will provide for the patient sitting in front of them. They arrive at these decisions after considering a host of clinical, psychosocial, and family issues; public policy is not part of the process. I am glad that, in the end, the FDA agreed with this sentiment and approved this agent as 1 more modest but real step toward improving the lives of people with cancer.

    Accelerated Approval for Bevacizumab: An Appropriate Decision »

    Why the FDA’s Approval of Bevacizumab Is Good News for Oncology Research »

    Creative FDA Clears Avastin For First-Line Breast Cancer »

  3. Pingback: bevacizumab

Leave a Reply

Your email address will not be published.