Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results.

Onapristone, a type-1 antiprogestin, has been tested for advanced breast cancer (BC), but its activity in early-stage, hormone receptor-positive, HER2-negative BC has not been fully explored. The ONAWA trial (ClinicalTrials.gov ID: NCT04142892- Registered on January 6, 2021) was a single-arm study evaluating the preoperative effects of onapristone with extended-release formulation (ONA-XR) (50 mg BID for 21 days) in postmenopausal women with Progesterone Receptor-positive (PgR+)/HER2-negative early BC. No complete cell cycle arrest (CCCA) was achieved at day 21, however ONA-XR significantly suppressed tumor proliferation with a Ki-67 geometric mean change of -17.78% (CI95 -39.76% to 12.20%) particularly in tumors with baseline PgR≥90% (-46.21%; CI -63.02% to -21.76%). Immunohistochemistry showed suppression of phospho-Ser294-PgR and p-STAT3, indicating effects on proliferation and endocrine pathways. Treatment also induced a shift to a more endocrine-sensitive phenotype. Of the 10 patients, 60% experienced adverse events, including one grade 3 increase in gamma-glutamyltransferase. In conclusion, ONA-XR showed early tumor proliferation suppression, particularly in high PgR-expressing tumors, supporting its potential for further clinical evaluation.