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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and Methods<\/jats:title>\n                    <jats:p>\n                      Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1\u201321 in combination with weekly P 80\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      123 subjects were randomized (62 to R\u2009+\u2009P and 61 to placebo\u2009+\u2009P). PFS was not different between the 2 groups (median 5.5 and 5.6\u00a0months for R\u2009+\u2009P and placebo\u2009+\u2009P, respectively; HR 1.13,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.5996). ALDH\n                      <jats:sup>+<\/jats:sup>\n                      and CD24\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/CD44\n                      <jats:sup>+<\/jats:sup>\n                      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\u2009\u2265\u20093 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration\/Date of Registration<\/jats:title>\n                    <jats:p>NCT01861054\/February 24, 2015.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10549-021-06367-5","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T15:18:29Z","timestamp":1630682309000},"page":"265-275","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["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)"],"prefix":"10.1007","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6542-3421","authenticated-orcid":false,"given":"Lori 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