{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:25:42Z","timestamp":1792034742207,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Selinexor (KPT\u2010330) is a potent inhibitor of exportin 1 (XPO1), in turn inhibiting tumor growth. Selinexor enhances the antitumor efficacy of eribulin in triple\u2010negative breast cancer (TNBC) in vitro and in vivo. Given the unmet medical need in TNBC and sarcoma, the authors explored the safety and efficacy of this combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors conducted a phase 1b trial of combined selinexor and eribulin using a 3\u00a0+\u00a03 dose\u2010escalation design in patients who had advanced solid tumors and in those who had TNBC in a dose\u2010expansion cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with TNBC (<jats:italic>N<\/jats:italic>\u00a0=\u00a019), sarcoma (<jats:italic>N<\/jats:italic>\u00a0=\u00a09), and other cancers (<jats:italic>N<\/jats:italic>\u00a0=\u00a03) were enrolled in the dose\u2010escalation cohort (<jats:italic>N<\/jats:italic>\u00a0=\u00a010) and in the dose\u2010expansion cohort (<jats:italic>N<\/jats:italic>\u00a0=\u00a021). The median number lines of prior therapy received was four (range, from one to seven prior lines). The most common treatment\u2010related adverse events for selinexor were nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%). One dose\u2010limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia. The recommended phase 2 dose was 80\u00a0mg of selinexor orally once per week and 1\u00a0mg\/m<jats:sup>2<\/jats:sup> eribulin on days 1 and 8 intravenously every 3\u00a0weeks. The objective response rate (ORR) was 10% in three patients. In the dose\u2010escalation cohort, the ORR was 10%, whereas six patients with had stable disease. In the TNBC dose\u2010expansion cohort (<jats:italic>n<\/jats:italic>\u00a0=\u00a018), ORR was 11%, and there were two confirmed partial responses with durations of 10.8 and 19.1\u00a0months (ongoing).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Selinexor and eribulin had an acceptable toxicity profile and modest overall efficacy with durable responses in select patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Effective therapies for advanced, triple\u2010negative breast cancer and sarcoma represent an unmet need.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Exportin 1 is associated with the transport of cancer\u2010related proteins.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Preclinical studies have demonstrated tumor growth inhibition and enhanced tumor sensitivity in patients who receive selinexor combined with eribulin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this phase 1b study, the authors evaluated the safety profile and clinical activity of the combination of selinexor, a potent oral inhibitor of exportin 1, and eribulin in patients with advanced cancers enriched for triple\u2010negative breast cancer or sarcoma.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The combination was well tolerated; most adverse events were mild or moderate, reversible, and managed with dose modifications or growth factor support.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The combination of selinexor and eribulin produced an antitumor response, particularly in some patients with triple\u2010negative breast cancer.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This work lays the foundation for prospective investigations of the role of selinexor and eribulin in the treatment of triple\u2010negative breast cancer.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34773","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T01:53:52Z","timestamp":1680659632000},"page":"2201-2213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phase 1b study of combined selinexor and eribulin for the treatment of advanced solid tumors and triple\u2010negative breast cancer"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8227-638X","authenticated-orcid":false,"given":"Blessie Elizabeth","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics 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