ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study with Letrozole, Palbociclib and Onapristone ER

Extended release Onapristone (Onapristone ER) is a progesterone receptor (PR) antagonist that inhibits hormone-mediated PR activation and stabilizes PR association with compressors, resulting in an antineoplastic effect when applied alone or in combination with antiestrogen therapy to breast cancer cells in vitro (1).

Recent preclinical studies further suggest that onapristone adds to inhibition of cell proliferation when combined with CDK4/6 inhibitors and fulvestrant (Figure 1; Unpublished).

Elevations in ctDNA can precede overt disease progression by several months in metastatic breast cancer and may represent an opportunity for proactive therapeutic intervention (2).