Abstract 4580: Improved quality of life and tumor regression in a patient with stage IV non-small cell lung cancer with brain metastasis 10 months after daily treatment with single agent mifepristone

The FDA granted an IND for a 40 patient study entitled “A phase II study of treatment with oral mifepristone as salvage therapy in patients with advanced or metastatic non-small cell lung cancer who have failed 2 or more previous chemotherapy or immunotherapy regimens”. Presented herein is a description of the effect of treating Case 1 who is a 68 year old male who presented with stage IV non-small cell lung cancer with brain metastasis causing seizures following 10 months of treatment with single agent oral mifepristone (Korlym from Corcept Inc) 300mg qd. He had shown tumor progression despite treatment with carboplatin, docetaxel, premetrexed, and gemcitabine. He was not considered a candidate for nivolumab or pembrolizumab because his tumor was negative for the programmed cell death factor ligand 1 (PD-L-1) marker. His preclinical performance status was ECOG 1. After 2 months of daily 300mg mifepristone treatment he showed a considerable improvement in energy and stamina and less shortness of breath. There have been no new lung or brain lesions. In fact, there has been shrinkage of the lung lesions and no growth of the brain lesion and no more seizures. His ECOG was “0” after 10 months of single agent mifepristone treatment. The mechanism of action is believed to be by suppressing intracytoplasmic production of an immunomodulatory protein known as the progesterone induced blocking factor (PIBF). One of the functions of PIBF is to stabilize perforin granules in natural killer cells thus inhibiting their cytotoxic activity. This protein seems to be unique to rapidly growing cells, e.g., trophoblast cells or cancer cells. Thus, in general, in low dosages, as used in this patient, the drug is very well tolerated. PIBF does not seem to be needed for cells growing at normal speed. In humans, mifepristone has been found to either cause complete tumor regression, or more commonly, stabilization of the cancer with improved quality of life. Previously, mifepristone allowed long-term complete remission from a terminal small cell lung cancer with associated hyponaotremia. The case reported here is believed the first involving palliative benefit of treating advanced non-small cell lung cancer with mifepristone. Stabilization of the brain metastasis in this report supports evidence from a previous case of advanced glioblastoma multiforme with a clear though transient response to mifepristone, that the drug can cross the blood-brain barrier, and thus be effective for brain lesions. This is the first case treated with 300mg daily mifepristone (200mg used previously). Similar to the lower dosage, this patient reported no adverse side effects. Mifepristone was also found to improve longevity and body conditioning scores in a placebo controlled study of spontaneous murine lung cancer. Citation Format: Jerome H. Check, Diane Check, Mahmoud Aly, Patricia Lofberg, Rachael Cohen, Dwight McKee. Improved quality of life and tumor regression in a patient with stage IV non-small cell lung cancer with brain metastasis 10 months after daily treatment with single agent mifepristone [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4580. doi:10.1158/1538-7445.AM2017-4580