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Baird, Richard D.; van Rossum, Annelot G.J.; Oliveira, Mafalda; Beelen, Karin; Gao, Meiling; Schrier, Mariette; Mandjes, Ingrid A.M.; Garcia-Corbacho, Javier; Vallier, Anne-Laure; Dougall, Greig; van Werkhoven, Erik; Linossi, Constanza; Kumar, Sanjeev; van Tinteren, Harm; Callari, Maurizio; Beddowes, Emma; Perez-Garcia, José-Manuel; Rosing, Hilde; Platte, Else; Nederlof, Petra; Schot, Margaret; de Vries Schultink, Aurelia; Bernards, René; Saura, Cristina; [...]

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients

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  • Medientyp: E-Artikel
  • Titel: POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients
  • Beteiligte: Baird, Richard D.; van Rossum, Annelot G.J.; Oliveira, Mafalda; Beelen, Karin; Gao, Meiling; Schrier, Mariette; Mandjes, Ingrid A.M.; Garcia-Corbacho, Javier; Vallier, Anne-Laure; Dougall, Greig; van Werkhoven, Erik; Linossi, Constanza; Kumar, Sanjeev; van Tinteren, Harm; Callari, Maurizio; Beddowes, Emma; Perez-Garcia, José-Manuel; Rosing, Hilde; Platte, Else; Nederlof, Petra; Schot, Margaret; de Vries Schultink, Aurelia; Bernards, René; Saura, Cristina; [...]
  • Erschienen: American Association for Cancer Research (AACR), 2019
  • Erschienen in: Clinical Cancer Research, 25 (2019) 22, Seite 6598-6605
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-19-0508
  • ISSN: 1078-0432; 1557-3265
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Abstract Purpose: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)–positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform–sparing PI3 kinase inhibitor. Patients and Methods: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a “rolling six” design. Results: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. Conclusions: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting.
  • Zugangsstatus: Freier Zugang