Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/172648
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dc.contributor.authorJuric, Dejan-
dc.contributor.authorRodon, Jordi-
dc.contributor.authorTabernero Caturla, Josep-
dc.contributor.authorJanku, Filip-
dc.contributor.authorBurris, Howard A.-
dc.contributor.authorSchellens, Jan H. M.-
dc.contributor.authorMiddleton, Mark R.-
dc.contributor.authorBerlin, Jordan-
dc.contributor.authorSchuler, Martin-
dc.contributor.authorGil-Martín, Marta-
dc.contributor.authorRugo, Hope S.-
dc.contributor.authorSeggewiss Bernhardt, Ruth-
dc.contributor.authorHuang, Alan-
dc.contributor.authorBootle, Douglas-
dc.contributor.authorDemanse, David-
dc.contributor.authorBlumenstein, Lars-
dc.contributor.authorCoughlin, Christina-
dc.contributor.authorQuadt, Cornelia-
dc.contributor.authorBaselga Torres, Josep, 1959--
dc.date.accessioned2020-12-09T16:40:33Z-
dc.date.available2020-12-09T16:40:33Z-
dc.date.issued2018-01-01-
dc.identifier.urihttps://hdl.handle.net/2445/172648-
dc.description.abstractPurposeWe report the first-in-human phase Ia study to our knowledge (ClinicalTrials.gov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase (PI3K)-selective inhibitor.Patients and MethodsIn the dose-escalation phase, patients with PIK3CA-altered advanced solid tumors received once-daily or twice-daily oral alpelisib on a continuous schedule. In the dose-expansion phase, patients with PIK3CA-altered solid tumors and PIK3CA-wild-type, estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer received alpelisib 400 mg once daily.ResultsOne hundred thirty-four patients received treatment. Alpelisib maximum tolerated doses were established as 400 mg once daily and 150 mg twice daily. Nine patients (13.2%) in the dose-escalation phase had dose-limiting toxicities of hyperglycemia (n = 6), nausea (n = 2), and both hyperglycemia and hypophosphatemia (n = 1). Frequent all-grade, treatment-related adverse events included hyperglycemia (51.5%), nausea (50.0%), decreased appetite (41.8%), diarrhea (40.3%), and vomiting (31.3%). Alpelisib was rapidly absorbed; half-life was 7.6 hours at 400 mg once daily with minimal accumulation. Objective tumor responses were observed at doses 270 mg once daily; overall response rate was 6.0% (n = 8; one patient with endometrial cancer had a complete response, and seven patients with cervical, breast, endometrial, colon, and rectal cancers had partial responses). Stable disease was achieved in 70 (52.2%) patients and was maintained > 24 weeks in 13 (9.7%) patients; disease control rate (complete and partial responses and stable disease) was 58.2%. In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, median progression-free survival was 5.5 months. Frequently mutated genes ( 10% tumors) included TP53 (51.3%), APC (23.7%), KRAS (22.4%), ARID1A (13.2%), and FBXW7 (10.5%).ConclusionAlpelisib demonstrated a tolerable safety profile and encouraging preliminary activity in patients with PIK3CA-altered solid tumors, supporting the rationale for selective PI3K inhibition in combination with other agents for the treatment of PIK3CA-mutant tumors.-
dc.format.extent12 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherAmer Soc Clinical Oncology-
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1200/JCO.2017.72.7107-
dc.relation.ispartofJournal of Clinical Oncology, 2018, vol. 36, num. 13, p. 1291-1299-
dc.relation.urihttps://doi.org/10.1200/JCO.2017.72.7107-
dc.rights(c) American Society of Clinical Oncology, 2018-
dc.sourceArticles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))-
dc.subject.classificationCàncer de mama-
dc.subject.classificationTiazoles-
dc.subject.classificationAssaigs clínics-
dc.subject.otherBreast cancer-
dc.subject.otherThiazoles-
dc.subject.otherClinical trials-
dc.titlePhosphatidylinositol 3-Kinase -Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.date.updated2020-12-02T14:17:46Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
dc.identifier.pmid29401002-
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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