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Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer
W Jonat1, T Bachelot2, T Ruhstaller3
1Department of Gynaecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Background:
The progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies.
Patients And Methods:
This randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer.
Results:
Patients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥ 35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥ 6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥ 6 months. Overall, 61 of 68 patients (90%) had ≥ 1 adverse event (AE), the most frequent (≥ 10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs.
Conclusion:
Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.
Insights
Lonaprisan demonstrated limited efficacy as a second-line endocrine therapy for metastatic breast cancer. The study did not meet its primary objective for clinical benefit rate in progesterone-receptor-positive patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Progesterone-receptor (PR) antagonists like onapristone and mifepristone have shown modest activity in hormone-receptor-positive breast cancer.
- Onapristone was linked to hepatotoxicity, prompting research into alternatives.
- Lonaprisan, a novel type III PR antagonist, was well-tolerated in earlier phase I studies.
Purpose of the Study:
- To evaluate the efficacy and tolerability of lonaprisan as a second-line endocrine therapy.
- To assess lonaprisan in postmenopausal women with advanced, PR-positive, HER2-negative metastatic breast cancer.
Main Methods:
- A randomized, open-label, phase II study.
- Postmenopausal women with stage IV, PR-positive, HER2-negative metastatic breast cancer were enrolled.
- Patients received either 25 mg or 100 mg of lonaprisan once daily.
Main Results:
- The primary objective, a clinical benefit rate of at least 35%, was not met.
- No complete or partial responses were observed.
- Stable disease for at least 6 months was achieved by 21% (25 mg group) and 7% (100 mg group).
- 90% of patients experienced at least one adverse event, most commonly fatigue, hot flush, and dyspnoea.
Conclusions:
- Lonaprisan exhibited limited efficacy as a second-line endocrine therapy for PR-positive metastatic breast cancer.
- Further investigation into lonaprisan's role in breast cancer treatment is warranted, considering its tolerability profile despite efficacy limitations.
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