Abstract 697: Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer, positive for the epidermal growth factor receptor (EGFR) mutation, that previously progressed on targeted therapy
Authors: Check Jerome H. , Check Diane , Poretta Trina , Aikins James , Wilson Carrie 
Published: September 2020

Abstract
Treatment with the oral single agent progesterone receptor modulator, mifepristone, has been demonstrated to significantly increase the quality and length of life in a patient with stage IV non-small cell lung cancer (NSCLC) that progressed despite multiple rounds of chemotherapy, when no markers existed for specific targeted therapy. The purpose of the present study was to determine if mifepristone could similarly provide palliative benefits to patients with NSCLC, that were positive for EGFR mutation, who had progressed despite targeted therapies. Patient 1, a 59 year old woman presented with 6 months of upper back pain and dyspnea, was found to have innumerable tiny lung nodules (miliary pattern), bone metastases, and a single brain metastasis (left occipital lobe). The tumor was an adenocarcinoma, with an EGFR exon leu858 arg identified. The brain metastasis was treated with palliative radiation therapy and erlotinib was started. She remained stable for 1 ½ years, but then her lung nodules started to increase in size. Erolotinib was stopped, and osimertinib was started. However, she progressed 6 months later, with continued growth of pulmonary nodules bilaterally and a new brain metastasis, in the right lateral cuneus. Her dyspnea, which had improved on erlotinib, returned to pre-treatment status. She was started on oral single agent mifepristone, 200mg per day. Patient 2, a 46 year old woman, had presented with headaches, difficulty with executive function, and memory loss. She was diagnosed with stage IV NSCLC, with extensive lung lesions and brain metastases. A MRI of the brain revealed innumerable supratentorial rim enhancing lesions, with one dominant left parietal lobe lesion measuring 3 × 2.1cm (treated with palliative radiation). CT scans showed innumerable bilateral pulmonary nodules with evidence of lymphangitic spread and multiple bone lesions. Because the tumor was positive for the EGFR1 exon 19 mutations (E746/751 mutation), she was started on afatinib, which was stopped 8 months later. She then had a second course of brain radiation and 5 months after stopping afatinib she began osimertinib. After 10 months of osimertinib, it seemed to be losing effectiveness, and so 200mg oral mifepristone was added. Both women have had stable disease, with no growth of previous nodules and no new nodules, or new brain metastases after 6 months and 14 months of mifepristone therapy, respectively. More importantly they both feel much better, with no dyspnea, or pain, and remain ECOG-0. Thus, similar to small cell lung cancer and NSCLC devoid of tumor markers, or with the PD-L1 mutation, patients with advanced NSCLC with EGFR mutation also seem to respond to the progesterone receptor modulator, mifepristone.
Citation Format: Jerome H. Check, Diane Check, Trina Poretta, James Aikins, Carrie Wilson. Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer, positive for the epidermal growth factor receptor (EGFR) mutation, that previously progressed on targeted therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 697.