Significant Palliative Benefits Following Therapy With Mifepristone for Advanced Treatment Resistant Small Cell Lung Cancer

Background/Aim: Progesterone receptor antagonists have been found to provide significant extension of life and considerable palliative benefits in a large variety of very advanced cancers. Most of these treated cancers lack the classical nuclear progesterone receptor (nPR). The hypothesized targets are membrane (m) PRs to inhibit progesterone induced blocking factor (PIBF). To date, there have been no case reports documenting the efficacy of PR antagonists for small cell lung cancer (SCLC) confirmed by pathological analysis. The case reported here demonstrates the efficacy of the single oral agent mifepristone in treating resistant SCLC. Case Report: A 58-year-old man, presenting with a persistent cough, dyspnea on exertion, and marked weakness, was diagnosed with stage IV non-SCLC (NSCLC) that tested positive for the EGFR mutation. He was treated with the single agent osimertinib. When symptoms returned eight months later, along with radiographic evidence of marked cancer progression, a lung biopsy showed SCLC. He failed to respond to pembrolizumab and subsequently to atezolizumab. He was then treated with the single agent mifepristone 200 mg per day orally. He showed marked clinical improvement associated with marked radiographic improvement. Though clinically doing very well, after one year, his dominant lesion increased in size. His oncologist elected to stop mifepristone and treat with camrelizumab with anlototinib. His clinical condition deteriorated on these drugs, and he died five months later. Conclusion: SCLC can be added to the long list of very advanced cancers that are treatment resistant to standard therapy, but respond well to PR antagonists.