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

Abstract

Purpose Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma. Patients and Methods Eligible patients were randomly assigned 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 were ascertained for all randomly assigned patients. On progression, patients receiving placebo could cross over and receive active drug. Results Among 164 eligible patients, 80 were randomly assigned to mifepristone and 84 to placebo. Twenty-four patients (30%) were able to complete 2 years of mifepristone without disease progression, adverse effects, or other reasons for discontinuation. Twenty-eight patients (33%) in the placebo arm completed the 2-year study. There was no statistical difference between the arms in terms of failure-free or overall survival. Conclusion Long-term administration of mifepristone was well tolerated but had no impact on patients with unresectable meningioma.

Mifepristone Extends Both Length and Quality of Life in a Patient With Advanced Non-small Cell Lung Cancer that Has Progressed Despite Chemotherapy and a Check-point Inhibitor

“…Most previous anecdotal cases were treated with a 200 mg dosage of mifepristone (1)(2)(3)(4). The drug was very well tolerated consistent with extensive data from patients that used it for the treatment of meningiomas (26). The case presented here, similarly to the first case in the study, showed that the 300 mg dosage of mifepristone is also well tolerated and relatively free of side effects.…”

Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539

“…10,21,25,27 The Southwest Oncology Group (SWOG-S9005) completed a phase III trial, published in 2015 by Ji and colleagues, assessing mifepristone, an antiprogestin. This study (SWOG-S9005) randomized patients with progressive or recurrent meningioma to receive either oral mifepristone or placebo, and found no improvement in either failure-free or overall survival with mifepristone.…”

“…This study (SWOG-S9005) randomized patients with progressive or recurrent meningioma to receive either oral mifepristone or placebo, and found no improvement in either failure-free or overall survival with mifepristone. 21 …”

Signaling the Unfolded Protein Response in primary brain cancers

“…However, the clinical results of mifepristone seem mitigated (Cossu et al, 2015;Ji et al, 2015). Further studies are needed to assess the role of ER stress in anaplastic meningiomas, but the rarity of such lesions limits wide cohort analysis.…”