AVASTIN – A Drug That Should Not Have Been Approved
In 2008, the FDA gave Avastin “accelerated approval” for breast cancer treatment on a “compassionate” basis. This was an injustice done to women with advanced breast cancer. A year before that, I predicted that this drug (and other drugs in its class) will prove to be failed drugs. On December 16, 2010, that prediction was validated. The FDA revoked its approval of Avastin declaring it ineffective.
Amazingly, the FDA based its approval of Avastin on a single clinical trial that failed to show any life extension with the drug. The company claimed that Avastin, when added to standard chemotherapy, slowed the progression of the disease for five and one half months for the median user. Not unexpectedly, two follow-up trials conducted by the manufacturer, Genentech, found that tumor progression was slowed for even shorter periods, from one to three months. More importantly, women with breast cancer failed to live longer in these trials as well. The company also admitted that the drug had caused serious adverse effects, including severe bleeding, stroke, heart problems, high blood pressure crisis, and holes in the gastrointestinal tract. The drug killed about one percent of the patients.
I raise four questions. First, should FDA approve any cancer drug when it is known not to extend life? Second, what does it mean when it is claimed that a drug slows the progress of cancer but does not prolong survival? Third, why did I predict in 2007 that Avastin and other drugs in its class will prove to be failed drugs? Fourth, recognizing that Avastin costs $100,000 or more per patient per year, are there other measures that cost less but might help the patient much more?
As to the first question, in my view it is inappropriate for the FDA to approve any cancer drug when it is known not to extend life. To date, all cancer drugs have proven to be toxic to most patients who take them, albeit to varying degrees. In many cases, toxicity of such drugs are disabling and long lasting. Toxicities of cancer drugs are considered acceptable trade-offs when the objective is significant life extension, even complete tumor eradication in many forms of childhood cancer and in the cases of a handfull of tumors in adults. However, the case of cancer drugs known to be completely ineffective in prolonging lives is different. One wonders how many patients would have agreed to take Avastin if they knew about its toxicity and its lack of efficacy.
As to the second question of the meaning of the claim that a drug slows tumor progression but does not extend life, to a pathologist it means that unreliable criteria are used to determine whether or not cancer is progressing. Tumor shrinkage seen with CAT, PET, and MRI scans is notoriously unreliable and generally does not indicate the capability of drugs taken to completely destroy all cancer cells. While such scans sometimes are helpful in choosing more desirable drugs, they do not by themselves alter the tumor biology in most cases.
The third question concerns the basis of my 2007 prediction that Avastin will prove to be a failed drug. Briefly stated, Avastin is supposed to inhibit new blood formation (angiogenesis), a phenomenon which is clearly a consequence of cancer metabolism, and not its cause. While writing my book entitled “The Crab, Oxygen, and Cancer Volume I: The Dysox Model of Cancer” (2007), I recognized a drug that blocks one of the consequences of cancer cannot be expected to provide good long term results. Tumors grow by different mechanisms and draw their growth requirements from normal cells they kill. So, the failure of Avastin to control cancer was entirely predicted—and, of course, was validated. I address the fourth question in a companion article entitled “Avastin: A Failed Drug,” (https://majidalimd.wordpress.com/2010/12/).
For a full discussion of the subject of tumor angiogenesis and the basis of my prediction of the failure of anti-angiogenesis drugs, I refer the readers to my book entitled “The Crab, Oxygen, and Cancer.”