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https://hdl.handle.net/2445/172648
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DC Field | Value | Language |
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dc.contributor.author | Juric, Dejan | - |
dc.contributor.author | Rodon, Jordi | - |
dc.contributor.author | Tabernero Caturla, Josep | - |
dc.contributor.author | Janku, Filip | - |
dc.contributor.author | Burris, Howard A. | - |
dc.contributor.author | Schellens, Jan H. M. | - |
dc.contributor.author | Middleton, Mark R. | - |
dc.contributor.author | Berlin, Jordan | - |
dc.contributor.author | Schuler, Martin | - |
dc.contributor.author | Gil-Martín, Marta | - |
dc.contributor.author | Rugo, Hope S. | - |
dc.contributor.author | Seggewiss Bernhardt, Ruth | - |
dc.contributor.author | Huang, Alan | - |
dc.contributor.author | Bootle, Douglas | - |
dc.contributor.author | Demanse, David | - |
dc.contributor.author | Blumenstein, Lars | - |
dc.contributor.author | Coughlin, Christina | - |
dc.contributor.author | Quadt, Cornelia | - |
dc.contributor.author | Baselga Torres, Josep, 1959- | - |
dc.date.accessioned | 2020-12-09T16:40:33Z | - |
dc.date.available | 2020-12-09T16:40:33Z | - |
dc.date.issued | 2018-01-01 | - |
dc.identifier.uri | https://hdl.handle.net/2445/172648 | - |
dc.description.abstract | PurposeWe 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.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Amer Soc Clinical Oncology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1200/JCO.2017.72.7107 | - |
dc.relation.ispartof | Journal of Clinical Oncology, 2018, vol. 36, num. 13, p. 1291-1299 | - |
dc.relation.uri | https://doi.org/10.1200/JCO.2017.72.7107 | - |
dc.rights | (c) American Society of Clinical Oncology, 2018 | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.classification | Tiazoles | - |
dc.subject.classification | Assaigs clínics | - |
dc.subject.other | Breast cancer | - |
dc.subject.other | Thiazoles | - |
dc.subject.other | Clinical trials | - |
dc.title | Phosphatidylinositol 3-Kinase -Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-12-02T14:17:46Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 29401002 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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JuricD.pdf | 878.28 kB | Adobe PDF | View/Open |
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