SWOG S9005: Double Blind Phase III Randomized Trial of the Anti-Progestin Agent Mifepristone in the Treatment of Unresectable Meningioma.

e17084 Background: Progesterone receptors are expressed on approximately 70 percent of meningiomas. Mifepristone is an oral anti-progestational agent that was reported to have modest activity in a phase II study. This multi-center, prospective, randomized, placebo-controlled, phase III trial conducted by SWOG was planned to define the role of Mifepristone as treatment of unresectable meningioma. Methods: Eligible patients were randomized to receive either Mifepristone or placebo for 2 years unless disease progressed. Patients who were stable or responding to protocol therapy after 2 years had the option to continue with the same blinded therapy. Serial follow-up allowed assessment of efficacy and toxicity. Time to treatment failure and overall survival was ascertained for all randomized patients. Upon progression, patients receiving placebo could crossover and receive active drug. Results: Among 164 eligible patients, 80 were randomized to Mifepristone and 84 to placebo arm. Twenty-four (30%) and 28 (33%) patients were able to complete the 2 years of Mifepristone or placebo, respectively, without disease progression, side effects, or other reasons for discontinuation. There was no statistical difference between the arms in terms of failure-free and overall survivals. None of the 41 patients who cross-over to Mifepristone, responded. Conclusions: Long term administration of Mifepristone is well tolerated but fails to improve survival in patients with unresectable meningioma. Clinical trial information: E-S9005.