Abstract 5835: Good quality sixty-eight percent 5-year survival in patients with treatment refractory stage IV lung cancer following treatment with a single agent progesterone receptor antagonist

Both the fetus and malignant tumors utilize membrane progesterone receptors (mPRs) to produce immunomodulatory proteins e.g., the progesterone induced blocking factor (PIBF) to escape immune surveillance. This study evaluated the efficacy of treating stage IV NSCLC or SCLC with single agent oral mifepristone 200-300mg/day. To be included, the cancer had to have progressed despite chemo or immunotherapy or the patient considered likely to die within 1 month. Six patients were evaluated, 4 with NSCLC, 2 with SCLC. Patients were not excluded for co-morbidities or if there were brain metastases. The patients completed a quality of life form every month for the first six months, then every third month, fourth, and six. 3 of 4 NSCLC patients had brain metastases and 2 had COPD with one considered end-stage COPD. 2 were positive for EGFR mutation, the other 2 had no markers to target. One of the two patients with SCLC had no prior therapy since her serum Na+ was 118 mmol/L and PO2 72 mmHg, with extremely rapid progressing SCLC. She was considered by her oncologist to be within two weeks of death with hospice recommended. All six patients showed marked palliative benefits even to the day they died. 3 of 4 with NSCLC lived 5+ years with one still alive. None showed any new metastases and many decreased in size. The 78-year-old woman with severe hyponatremia had a serum Na +of 145 mmol/L and serum PO2 of 100 mmhg one month after treatment and eventually went into full remission. She died at the age of 83 with myocardial infraction with no evidence of cancer. The 68-year-old woman with end stage COPD died after 1.5 years from COPD with her cancer stable from COPD. The 68-year-old male with COPD died at age 73 with pneumonia during the COVID pandemic. His cancer was relatively stable with just slight growth of his primary lung lesion. Both women with NSCLC EGFR + lived five years despite not starting mifepristone until 1 year after treatment with Osimertinib when the cancer was now rapidly progressing with the presence of multiple brain metastasis. One died, but her cancer was stable. We could not ascertain the cause of death. The 65-year-old male with SCLC was clinically doing well after 1 ½ years of mifepristone. However, because the lesions were still present (but smaller) his oncologist enrolled him in a clinical trial requiring him to stop the mifepristone. He died 3 months later. Though some studies find with the new therapies available some patients with stage IV NSCLC may have a 15% 5-year survival from first diagnosis. Though there were only 6 patients in this study, this excellent 5-year survival outcome in previously treated or terminal patients with NSCLC or SCLC strongly suggests the efficacy of single agent mifepristone for advanced lung cancer with no more treatment options available. Citation Format: Jerome H. Check, Diane Check, Carrie Wilson, Maddison Neulander. Good quality sixty-eight percent 5-year survival in patients with treatment refractory stage IV lung cancer following treatment with a single agent progesterone receptor antagonist [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5835.