July 15, 2009—FDA Testimony Opposing the Approval of Doxil for Metastatic Breast Cancer
Statement in Opposition to NDA 50-718Wednesday, July 15, 2009
My name is Vernal Branch. I am here today as a concerned consumer advocate on behalf of Breast Cancer Action (BCA). BCA is a national education and advocacy organization with over 30,000 members. We would like for this panel to consider certain criteria before approving Doxil for metastatic breast cancer.
In light of the number of drugs already approved to treat breast cancer, BCA believes that certain standards should be followed by the FDA when considering an application for an additional treatment for the disease. Any drug approved at this time should:
• Extend the lives of patients – improve overall survival, and/or
• Improve patients’ quality of life
Applying this standard to the application under consideration clearly indicates that Doxil should not be approved for the treatment of metastatic breast cancer.
The data show that there is no overall survival benefit from the use of Doxil in this setting. There are clearly options for avoiding increased cardio-toxicity following treatment with anthracyclines that do improve survival. Those options are shown in the staff briefing for this discussion in table 3.
The focus of the applicant is on incremental improvement. From a patient perspective, this is simply no longer good enough.
In addition, Doxil was shown to have poor tolerability with many side effects, including neutropenia (66%), stomatitis (50%), and hand – foot syndrome (61%) These side-effects substantially reduce quality of life for patients and are the reason for the 34% rate of early discontinuation in the BCA 3001 trial.
We also note with dismay the change in primary endpoints in the single trial that is the focus of this application. The shift from an overall all survival endpoint to a time- to-progression end point seems to accommodate the need for the applicant to show some benefit, when there is none in the outcome of most concern to patients. Even if TTP were an appropriate endpoint, we are deeply concerned about the lack of reliability in the determination of TTP by those who independently reviewed patient status, as reported by the applicant.
With so many other therapies available for this group of patients we feel that this drug should not be approved with little or no benefit for overall survival and significant adverse events.
As a matter of policy, in order to avoid the fact or appearance of a conflict of interest, Breast Cancer Action does not accept funding from Ortho Biotech or from any other pharmaceutical or biotech company.