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

Ann Oncol. 2013 Oct;24(10):2543-2548. doi: 10.1093/annonc/mdt216. Epub 2013 Jun 20.


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.

Trial registration: ClinicalTrials.gov NCT00555919.

Keywords: antiprogestin; breast cancer; lonaprisan; progesterone-receptor antagonist; progesterone-receptor positive.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Estrenes / adverse effects
  • Estrenes / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Receptors, Progesterone / antagonists & inhibitors*
  • Receptors, Progesterone / metabolism
  • Treatment Outcome


  • Antineoplastic Agents, Hormonal
  • Estrenes
  • Receptors, Progesterone
  • lonaprisan

Associated data

  • ClinicalTrials.gov/NCT00555919