dc.contributor.author | Sarker, D | |
dc.contributor.author | Dawson, NA | |
dc.contributor.author | Aparicio, AM | |
dc.contributor.author | Dorff, TB | |
dc.contributor.author | Pantuck, AJ | |
dc.contributor.author | Vaishampayan, UN | |
dc.contributor.author | Henson, L | |
dc.contributor.author | Vasist, L | |
dc.contributor.author | Roy-Ghanta, S | |
dc.contributor.author | Gorczyca, M | |
dc.contributor.author | York, W | |
dc.contributor.author | Ganji, G | |
dc.contributor.author | Tolson, J | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2021-10-20T09:40:35Z | |
dc.date.available | 2021-10-20T09:40:35Z | |
dc.date.issued | 2021-10-01 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2021 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4835 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-21-1115 | |
dc.description.abstract | PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR)-targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory PTEN activates PI3K/AKT signaling and contributes to resistance to androgen deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance. PATIENTS AND METHODS: In this phase I study (NCT02215096), patients with PTEN-deficient mCRPC who progressed on prior enzalutamide received once-daily enzalutamide 160 mg plus PI3Kβ inhibitor GSK2636771 at 300 mg initial dose, with escalation or de-escalation in 100-mg increments, followed by dose expansion. Primary objectives were to evaluate safety/tolerability, determine the recommended phase II dose, and assess the 12-week non-progressive disease (PD) rate. RESULTS: Overall, 37 patients were enrolled; 36 received ≥1 dose of GSK2636771 (200 mg: n = 22; 300 mg: n = 12; 400 mg: n = 2) plus 160 mg enzalutamide. Dose-limiting toxicities occurred in 5 patients (200 mg: n = 1; 300 mg: n = 2, 400 mg: n = 2). No new or unexpected adverse events or evidence of drug-drug interaction were observed. At the recommended dose of GSK2636771 (200 mg) plus enzalutamide, the 12-week non-PD rate was 50% (95% confidence interval: 28.2-71.8, n = 22); 1 (3%) patient achieved a radiographic partial response lasting 36 weeks. Four of 34 (12%) patients had prostate-specific antigen reduction of ≥50%. CONCLUSIONS: Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.title | A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-07-14 | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-21-1115 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2022-07-19 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | De Bono, Johann | |