Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer

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. 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. 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. Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.