Application to FDA for Approval of Olaparib to Treat BRCA + Ovarian Cancer
Read our full testimony to the ODAC Committee.
Stay tuned for updates on the FDA's decision in the next few months.
FDA's Oncologic Drugs Advisory Committee (ODAC) Meeting on Approval of Olaparib for Hereditary Ovarian Cancer
Read our full testimony presented at the ODAC meeting June 25.
PARP inhibitors are agents that were developed specifically for the treatment of cancers associated with a BRCA genetic mutation. FORCE first learned about PARP inhibitors such as olaparib a decade ago; since that time, we have followed the research, educated our community about these agents, generated excitement about the research focus on HBOC, and facilitated clinical trial enrollment.
Although members of the BRCA community are very motivated to participate in research, completion of PARP inhibitor studies has taken a long time and in the duration, many women who could not access PARP inhibitors and did not meet criteria for any clinical trial have died of hereditary cancers. Published research on PARP inhibitors for hereditary ovarian cancer has been encouraging. Based on this research, AstraZeneca, the company that manufactures olaparib has applied for FDA approval of the drug as maintenance therapy for platinum-sensitive ovarian cancer in women with BRCA mutations.
FDA's ODAC Meeting
On June 25, 2014 the Oncologic Drugs Advisory Committee (ODAC) of the FDA met to discuss AstraZeneca Pharmaceuticals’ new drug application for olaparib (a PARP inhibitor) capsules as maintenance treatment of patients with platinumsensitive relapsed ovarian cancer who have completed chemotherapy. The public meeting took place at the FDA offices outside of Washington, D.C. The FDA released their analysis of the research in advance of the ODAC meeting. They recommended waiting until the completion of further studies before approving the drug. On June 25 at the hearing, ODAC voted 11 -2 in favor of delaying olaparib approval until the current clinical trials are completed.
What is FORCE's position on this issue?
FORCE is extremely disappointed with ODAC's decision. We have been a strong proponent of PARP inhibitor research, and we strongly support immediate FDA approval of olaparib based on the available research. We are concerned that many women will die of hereditary ovarian cancer while we wait for studies to be completed. We asked ODAC and the FDA to consider these points in considering the application:
- Ledermann and colleagues published the outcomes for BRCA-mutation carriers in the Phase II olaparib maintenance trials in Lancet Oncology1. Olaparib showed a significant effect on progression-free survival and time to subsequent therapy in BRCA-mutation carriers, with a median time of 15.6 months in patients receiving olaparib versus 6.2 months in the placebo group.
- The trend towards survival favors women who took olaparib, with 55% of patients in the placebo arm dying compared to 50%, with a reported hazard ratio of 0.73.
- The adverse effects reported appear to be manageable.
- As of January 2014, 20 patients remained on study and of those, 19 were in the olaparib group. In addition, 18% of all patients in the olaparib group received the drug for over 3 years.
- Platinum hypersensitivity or intolerance has been shown to occur in 20-40% of patients treated with cisplatin or carboplatin, increasing with repeated exposures, which limits their. Many patients have moderate to severe side-effects on platinum-containing drugs. It is imperative to have less toxic non-platinum treatment options available for women with hereditary ovarian cancer.
- Olaparib gives BRCA mutation carriers with ovarian cancer more time without disease and more time where they can avoid chemotherapy, translating to months or years with improved quality of life.
What does this mean for our community?
The FDA is expected to make a final ruling on this application in October. Although unlikely, the FDA could still approve this application for olaparib as maintenance therapy for women with advanced, BRCA + ovarian cancer. If approved, oncologists would be able to prescribe olaparib for these patients. People with BRCA mutations and advanced cancers of any type who do not qualify for any clinical trial or research study may be able to get access to olaparib if prescribed "off-label" by their oncologist. Approval of the agent could facilitate further development of new and better targeted agents for people with BRCA mutations.
If the FDA rules against approval of olaparib, only those who qualify for participation in clinical trials will have access to this agent. Further applications for FDA approval may be filed after the completion of these clinical trials which could take several more years.
1. Ledermann, J. Harter, P. et. al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase II trial. Lancet Oncology, May 30, 2014. Epublished ahead of print.
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