A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida)

• DOI: 10.1007/s10549-021-06367-5
• Publication Date: 2021-09-03T19:18:29Z
• Authors: Lori J. Goldstein; Mauro Mansutti; Christelle Levy; Jenny C. Chang; Stephanie Henry; Isaura Fernandez-...; Jana Prausovà; Elzbieta Starosla...; Giuseppe Viale; Beth Butler; Susan McCanna; Pier Adelchi Ruffini; Max S. Wicha; Anne F. Schott; ; Ricardo H. Alvarez; Anne F. Schott; Maysa Abu-Khalaf; Nuhad Ibrahim; Brooke Daniel; Michael Meshad; David Kanamori; Amelia Zelnak; Mark Graham; Jason Comer; Manon Huizing; Francois Duhoux; Vincent Richard; Didier Verhoeven; Martin Smakal; Marta Krasenska; Milan Kohoutek; Martina Zimovjanova; Eugen Kubala; Mario Campone; Jean-Marc Ferrero; Anthony Goncalves; Laurence Venat-Bo...; Jacques Medioni; Laura Biganzoli; Hector Soto Parra; Paolo Pedrazzoli; Marco Colleoni; Mauro Moroni; Dino Amadori; Paolo Morandi; Saverio Cinieri; Piotr Tomczak; Tomasz Sarosiek; Marek Wojtukiewicz; Andrzej Mruk; Bożena Kukielka-B...; Silvia Antolin Novoa; Estela Vega Alonso; Miguel Martin Jim...
• Keywords: Clinical endpoint; Triple-negative breast cancer; Combination therapy

Abstract Purpose CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor was safely administered to metastatic patients in combination with paclitaxel (P) and appeared reduce CSC window-of-opportunity trial operable cancer. The fRida (NCT02370238) evaluated addition R weekly first-line therapy (m) TNBC. Subjects Methods untreated mTNBC were randomized 1:1 or placebo days 1–21 P 80 mg/m 2 1, 8, 15 28-day cycles. primary endpoint PFS by central review. Results 123 subjects (62 + 61 P). not different between groups (median 5.5 5.6 months P, respectively; HR 1.13, p = 0.5996). ALDH CD24 − /CD44 centrally IHC found 16 34 54 who provided tissue biopsy at study entry. Serious adverse events (21.3 20% subjects) grade ≥ 3 reactions (ADR) (9.1 6.3% all ADRs) occurred similar frequency both groups. Conclusion is first randomized, double-blind clinical CSC-targeting agent chemotherapy prolonged met. Clinical Trial Registration/Date Registration NCT01861054/February 24, 2015.