Abstract 1032: Progesterone receptor antagonist can provide marked palliative benefits and extend life by years in advanced lung cancer when no other treatment options are available
Authors: Check Jerome H. , Check Diane , Poretta Trina 
Published: June 2022

Abstract
Metastatic lung cancer has a poor prognosis. The aim of chemotherapeutic agents, targeted therapies, or immunotherapies at this stage is to extend life and diminish suffering. Frequently the extension of life is for a few months, but amelioration of suffering is not always accomplished including side effects of medication. Mifepristone, a progesterone (P) receptor modulator/antagonist has been given to patients orally (200-300 mg/day) with Food and Drug Administration (FDA) approval to patients with advanced metastatic lung cancer that had no more treatment options. Several of these cases have been presented at the AACR and showed significant extension of a good quality of life with well tolerated mifepristone therapy (Case 1 - rapidly progressing probable small cell lung cancer (SCLC) with marked hypoxia and marked hyponatremia, AACR 2016; Case 2 - Stage IV non-small cell lung cancer (NSCLC) with brain metastasis with no tumor markers for targeted therapy, AACR 2017; Case 3 - NSCLC positive for programmed cell death protein 1 (PD-1), AACR 2018). In case 1 her PO2 and serum sodium normalized within 3 weeks of single agent mifepristone and her lung nodules were no longer detectable. At time of presentation in 2016 she was 3 ½ years on single agent mifepristone treatment. She died 5 years from treatment at age 85 from a myocardial infarction with no return of her lung cancer and normal serum sodium. Case 2 also received single agent mifepristone and had no new lung or brain lesions (predominantly stable disease), but he stated he felt perfectly normal. After 2 ½ years his primary lung lesion started growing slowly. He died 5 years later not from extensive lung cancer but from pneumonia complicating his chronic obstructive lung disease (COPD). Case 3 had progressed despite standard chemotherapy and nivolumab. With mifepristone her lung and brain metastases showed some regression, but she was enjoying a good quality of life. Her clinical status deteriorated after 1 year not from her cancer but worsening COPD and she died 1 ½ years after initiating mifepristone therapy. Two female cases (age 56 and 46) that were never presented at AACR were treated with mifepristone when their advanced lung cancer with brain metastases progressed despite the third-generation tyrosine kinase inhibitor osimertinib (they were positive for the EGFR mutation). These women had a good quality of life and are still alive after 4 years of treatment. Evidence suggests that mifepristone inhibits cancer by blocking membrane P receptors inhibiting the immunosuppressive protein called the progesterone induced blocking factor. The “parent” 90 kDa form helps the tumor to proliferate and invade normal tissue whereas smaller splice variants inhibit cellular immunity. Mifepristone may actually be more effective for cancers negative for the classical nuclear P receptor.
Citation Format: Jerome H. Check, Diane Check, Trina Poretta. Progesterone receptor antagonist can provide marked palliative benefits and extend life by years in advanced lung cancer when no other treatment options are available [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1032.