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)
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Published:2021-09-03
Issue:2
Volume:190
Page:265-275
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ISSN:0167-6806
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Container-title:Breast Cancer Research and Treatment
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language:en
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Short-container-title:Breast Cancer Res Treat
Author:
Goldstein Lori J.ORCID, Mansutti Mauro, Levy Christelle, Chang Jenny C., Henry Stephanie, Fernandez-Perez Isaura, Prausovà Jana, Staroslawska Elzbieta, Viale Giuseppe, Butler Beth, McCanna Susan, Ruffini Pier Adelchi, Wicha Max S., Schott Anne F., Alvarez Ricardo H., Schott Anne F., Abu-Khalaf Maysa, Ibrahim Nuhad, Daniel Brooke, Meshad Michael, Kanamori David, Zelnak Amelia, Graham Mark, Comer Jason, Huizing Manon, Duhoux Francois, Richard Vincent, Verhoeven Didier, Smakal Martin, Krasenska Marta, Kohoutek Milan, Zimovjanova Martina, Kubala Eugen, Campone Mario, Ferrero Jean-Marc, Goncalves Anthony, Venat-Bouvet Laurence, Medioni Jacques, Biganzoli Laura, Parra Hector Soto, Pedrazzoli Paolo, Colleoni Marco, Moroni Mauro, Amadori Dino, Morandi Paolo, Cinieri Saverio, Tomczak Piotr, Sarosiek Tomasz, Wojtukiewicz Marek, Mruk Andrzej, Kukielka-Budny Bożena, Novoa Silvia Antolin, Alonso Estela Vega, Jimenez Miguel Martin,
Abstract
Abstract
Purpose
CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC.
Subjects and Methods
Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1–21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review.
Results
123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24−/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups.
Conclusion
fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met.
Clinical Trial Registration/Date of Registration
NCT01861054/February 24, 2015.
Funder
Dompé farmaceutici s.p.a., Milano, Italy National Cancer Institute- Fox Chase Cancer Center Core Grant
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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