دورية أكاديمية
Phosphatidylinositol 3-Kinase -Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study
| العنوان: | Phosphatidylinositol 3-Kinase -Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study |
|---|---|
| المؤلفون: | Juric, Dejan, Rodon, Jordi, Tabernero Caturla, Josep, Janku, Filip, Burris, Howard A., Schellens, Jan H. M., Middleton, Mark R., Berlin, Jordan, Schuler, Martin, Gil-Martín, Marta, Rugo, Hope S., Seggewiss Bernhardt, Ruth, Huang, Alan, Bootle, Douglas, Demanse, David, Blumenstein, Lars, Coughlin, Christina, Quadt, Cornelia, Baselga Torres, Josep, 1959- |
| المصدر: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
| بيانات النشر: | Amer Soc Clinical Oncology |
| سنة النشر: | 2018 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Càncer de mama, Tiazoles, Assaigs clínics, Breast cancer, Thiazoles, Clinical trials |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 12 p.; application/pdf |
| اللغة: | English |
| العلاقة: | Reproducció del document publicat a: https://doi.org/10.1200/JCO.2017.72.7107Test; Journal of Clinical Oncology, 2018, vol. 36, num. 13, p. 1291-1299; https://doi.org/10.1200/JCO.2017.72.7107Test; http://hdl.handle.net/2445/172648Test |
| الإتاحة: | https://doi.org/10.1200/JCO.2017.72.7107Test http://hdl.handle.net/2445/172648Test |
| حقوق: | (c) American Society of Clinical Oncology, 2018 ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.8840F1D8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |