On July 9, 2014, the FDA denied the Citizen Petition filed by Steven Zecola for it to withdraw support of ACT chemotherapy for BRCA1 breast cancer patients. The core of the FDA’s rationale is that: “Available evidence indicates that ACT drugs approved for the treatment of breast cancer are effective in BRCA1 TNBC patients”. See Denial at page 9. For support of this finding, the FDA references Lee L.J., B Alexander, et al., 2011, “Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers”, Cancer, 3093-3100.
However, the FDA fails to recognize that this study finds: “the 10-year survival rates for women who received adjuvant chemotherapy were 71% for carriers [and]….Among women who did not receive chemotherapy, the 10-year survival rates were 75% for carriers…” That is, the survival rates were better for BRCA1 carriers who did not take chemotherapy.
The FDA makes several other critical omissions. For example, it says: “There is no standard targeted treatment for TNBC (with or without a BRCA1 mutation)”. However, the above study notes that “the majority of chemotherapy regimens contained an anthracycline backbone (91%), most commonly doxorubicin and cyclophosphamide (AC), doxorubicin, cyclophosphamide, 5- fluoruracil (CAF) or doxorubicin, cyclophosphamide followed by paclitaxel (AC+T). Additionally, the National Comprehensive Cancer Network recommends ACT for TNBC.
The FDA also fails to recognize a critical finding of the above report, namely, “In a recent report of 102 women with BRCA-1 related breast cancer, the pathologic complete response (CR) rate for 12 patients treated with neo-adjuvant cisplatin on a clinical study was 83%, compared to 22% for the 51 BRCA1 mutation carriers who received AC in a retrospective comparison.”
The FDA also dismisses the disproportional side effects of ACT chemotherapy by saying: “There are side effects with all chemotherapeutic agents (not just ACT).” However, as I pointed out in the Petition: “These chemicals also cause hair loss, nausea, and pain among many other unpleasant side effects, including increased emotional stress”. Platinum-based agents do not have nearly as many or as severe side effects. The impact of side effects should be included in the decision to authorize drugs as well as in comparing one drug versus another.
The FDA says that the Petition did “not presented any evidence suggesting that side effects are more deleterious in BRCA1 patients being treated with ACT drugs than in other patients”. However, that is the wrong standard and wrong comparison. The relevant treatment choices for BRCA1 breast cancer patients after surgery are: ACT, Carboplatin/Parp inhibitors (currently in clinical trials), or no chemotherapy. ACT provides the poorest outcome of these options and the worst side effects. These are the proper measures that the FDA should be considering in comparing treatment options.
Because of the FDA’s shortsightedness, 15,000 women with BRCA1-related breast cancer will be prescribed a regimen of ACT chemotherapy each year for the next several years until carboplatin and Parp Inhibitors overcome the obstacles of the regulatory process.
It is clear why the current FDA process benefits the incumbent pharmaceutical companies. It is not clear how the process — which is designed to protect the status quo — benefits the public.
The conflict between regulation and technological advancement will increase as the FDA’s regulatory strait-jacket is applied to the growing number of solutions derived from the application of “big data” correlations to individual genetic information to derive new solutions.
The solution requires political action, but it will not be coming from the FDA.