Sounding Board: Controversy Surrounding the FDA Approval of Avastin

Published: Monday, Apr 14, 2008
The recent FDA accelerated approval for Avastin (bevacizumab), in combination with paclitaxel chemotherapy for the treatment of patients who have not received chemotherapy for their metastatic HER2-negative breast cancer, has sparked larger discussion about the approval of pharmaceuticals that may improve quality of life but do not necessarily extend life. Below are the thoughts of three OncNG editorial board members:

Maurie Markman, MD

Unfortunately, the discussion regarding the utility of bevacizumab has failed to differentiate between benefit defined by evidence-based (randomized phase III) clinical trial data and the actual cost of that therapy. While the highly statistically significant improvement in the time to clinical disease progression demonstrated in this trial will certainly not be of relevance to all patients in this setting, it will be to many—and perhaps most—individuals.

Of great importance in this discussion, cost is not defined by “scientific evidence,” but rather by the “marketplace.” As a society, we absolutely must deal with the issue of the staggering costs of oncology drugs. But in this discussion, we should not permit these legitimate concerns about cost to negate the documented benefits to quality of life as revealed in well-conducted, evidence-based clinical trials. It is absolutely acceptable to declare, “We can’t afford this drug at its current cost.” Conversely, it is inappropriate to state, “This drug did not impact a meaningful clinical outcome in women with breast cancer.”

E. Roy Berger, MD, FACP

Lately, disease-free survival, or progression-free survival (PFS), has sometimes worked and other times not worked when it comes to predicting survival. My feeling is that in today’s marketplace, in which drugs and medical oncology are so expensive, it’s very difficult to approve a lot of drugs. My personal preference is that metastatic disease survival should be the endpoint, rather than PFS. The pro to that is that you’ll get drugs that show survival differences. The con is that it’s going to take some drugs a long time to reach that endpoint.

PFS had, in a number of cases, predicted survival differences. Now that we’ve seen a number of drugs in which there were survival diff erences but no PFS, it creates a big question mark. It’s going to be more expensive to reach survival diff erences and thereby possibly drive the prices of those drugs up when they do get approved, but they will also eliminate a lot of drugs that might have been approved based on PFS that don’t reach survival diff erences. Another way to do it would be to approve drugs based on PFS but withdraw the approval if they don’t show survival diff erences. That way, patients can get earlier access to drugs that look like they are going to show a survival difference and also avoid those drugs being on the market long-term if they don’t.

For example, Provenge missed its mark of PFS by 0.07; in two trials, it did show a survival diff erence, and the FDA advisory board advised that the FDA approve it. But then a month later, it was not approved. So, the FDA gave an approvable letter saying that “as soon as you show us a survival difference” in the IMPACT study that they’re doing now, “we’ll approve you.” Many cancer patients were upset that they couldn’t get access to the drug. A lot of people could have benefi ted from it, but they didn’t because it wasn’t approved. Now, you take Avastin, and for one reason or another, that was approved based on PFS, but no survival diff erence was shown in breast cancer.

Should a drug like Avastin that does not show a survival diff erence be approved? My feeling is that it’s too expensive, there are toxic eff ects from it, and I’m not sure it’s the right thing to do. I wouldn’t prescribe it to my patients with metastatic breast cancer. I think that the approval of Avastin sets a precedent. How can you tell one company for whom you approve a very expensive drug based on PFS and not survival diff erence “yes” and tell another company “no”?  I think we’re spending way too much on the last three months of life and that we’re going to have to ration healthcare.  So, if you have a 25- or 30-year-old woman who could use something like Avastin to improve PFS, we can consider that if we can stop having secondary and tertiary lung cancer patients, let’s say, who are 85 years old getting chemotherapy when we’ve shown that there’s very, very little chance of helping them.

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