It is official. The FDA revoked approval of Avastin™(bevacizumab) to treat breast cancer. This issue has been discussed here and here because there has been some speculation that the FDA decision examined the costs in addition to risks and benefits.
In clinical trials, including the one which lead to accelerated FDA approval, there was an 5 1/2 month average delay in progression of disease. Subsequent trials were not even that positive, suggesting an average of 1 1/2 – 3 months of delayed progression of disease. A mortality benefit could not be demonstrated in these trials.
Avastin is a nasty drug with a significant side effect profile including risk of bowel perforation and fistula formation and hypertension.
So rather than opine in a vacuum, Dr. J. went to one of his breast cancer specialist friends for her opinion.
Her reaction was mixed. On the one hand, it is not the most efficacious choice and it has hideous side effects. Furthermore, while there are rare patients who respond very well to the therapy, we have no way of predicting response prior to initiating this therapy. By way of contrast, we are now developing cancer therapies that are tailored to individual tumor profiles (i.e., if gene x is + then treatment x, if gene y is + then treatment y). Her concern was for her handful of patients who are responding to this therapy, or might respond in the future when other therapies fail.
Writing a drug for an off label indication is no big deal. It is done ALL THE TIME with generic medications (the most obvious in Dr. J.’s mind is the use of amiodarone or a legion of generic antiarrhythmics for atrial fibrillation). Avastin, however is a biologic medication (a modified antibody), and thus is very expensive. By having the indication pulled, CMS and insurance companies are unlikely to pay for it. So while the oncologist might prescribe it, if the patient’s insurance won’t pay, than either the patient, or the drug company will be on the hook.
Now the doctor and the patient can argue that there is a clinical response to Avastin plus taxol, but the payor can rebut that argument with, ‘How do you know it isn’t the taxol?’ which is a fair argument because we can’t look into the alternate timeline next door to see how the same patient did in that timeline on taxol alone. The answer simply is, the patient is on BOTH and BOTH are working.
If Dr. J. were on the FDA, and he never will be in all likelihood, he would have perhaps altered the label to further emphasize that risk/benefit be weighed, but he would have let it be available. It would be up to CMS and insurance companies to decide if the risk/benefit and cost/benefit are worth it. Perhaps we would eventually identify a biomarker that predicts response, but with the label pulled, obtaining funding to further refine the target population seems extremely unlikely. Fortunately, there are a number of therapies and therapeutic strategies in the pipeline, so there is still hope for many.
Dr. J. just prays for the well being of patients who are Avastin responders as the effects of the label change unfold.