Comments submitted to Food and Drug Administration Oncology Drug AdvisoryCommittee (ODAC) meeting on December 16, 2008
C3: Colorectal Cancer Coalition is a non-profit, nonpartisan advocacy organizationcommitted to winning the fight against colon and rectal cancer through research,empowerment and access.C3 believes in fully disclosing sources of financial support. C3 receives funding from both Bristol Myers Squibb and Amgen in the form of charitable donations. Additionally,in 2008, C3 received a charitable grant from Caris Diagnostics, a company that testscolorectal cancer tumors for the KRAS mutation. None of these companies nor any of our other corporate supporters has influenced our comments on this issue.On page 3 of the FDA Briefing Document, FDA listed the requirements they laid for submission of KRAS data.In theory, these are good requirements and could be applied to both KRAS and future biomarkers and companion diagnostics.However, we feel that the requirements fail to take into account the fact that there aremany approved drugs on the market. As we speak, researchers are mining bankedtissues, looking for markers thatwill help target those drugs most effectively. Some of that research may yield gems thatwill help patients avoid toxicity, or increase likelihoodof benefit from treatment. However, while current and ongoing trials routinely bank high proportions of tissue, past trials did not. Thus, a requirement that tissue be availablefrom 90-95% of participants in a single trial means that tissue from past trials will belargely useless for submissions.In this era of personalized medicine, C3 strongly believes that we must be cautious aboutone-size-fits-all requirements. We believe that tissue and assay requirements vary, andthat the following types of questions should be considered:
What do we know about the biomarker? Are the results consistent with what weknow about themechanism of action? Do we know what percentage of patients inthe general population have this biomarker?
What do we know about the assay? Does the assay involve new technology? Arethe assay results subjective, such as in a gene expression test, or are theyobjective, such as in a gene mutation test? Do they require “black box”calculations such as OncotypeDX?
Are the clinical results consistent across analyses of multiple datasets?
What is the strength of the clinical impact on patients? Do patients with a specific biomarker respond more to a specific drug? Less? Not at all?