UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Glucocorticoid regimen options in combination with abiraterone acetate: an international, multicenter, randomized, open-label phase 2 study

Attard, G; (2019) Glucocorticoid regimen options in combination with abiraterone acetate: an international, multicenter, randomized, open-label phase 2 study. JAMA Oncology (In press).

[img] Text
JAMA Onc_Abi Steroids_combined.pdf - Accepted version
Access restricted to UCL open access staff until 3 February 2020.

Download (1MB)

Abstract

Importance Abiraterone acetate is combined with prednisone 5 mg twice daily (BID) for metastatic castration-resistant prostate cancer (mCRPC) and with prednisone 5 mg QD for newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer. Understanding the physiological effects of these and other regimens is important. Objective To evaluate the safety of abiraterone acetate with four glucocorticoid regimens. Design Open-label, randomized (1:1:1:1), clinical trial in men with mCRPC. Setting Twenty-two hospitals in 5 countries. Participants Of 204 men screened, 164 were randomly assigned between June 2013 and October 2014. Intervention Abiraterone acetate 1000 mg QD with prednisone 5 mg BID (n=41), 5 mg QD (n=41), 2.5 mg BID (n=40), or dexamethasone 0.5 mg QD (n=42). Main Outcome and Measure The primary endpoint was no mineralocorticoid excess (grade ≥1 hypokalemia or grade ≥2 hypertension) through 24 weeks (6 cycles). Results In the prednisone 5 mg BID, QD, and 2.5 mg BID, and dexamethasone groups, respectively, 70.6% (95% CI, 53.8%-83.2%), 36.8% (95% CI, 23.4%-52.7%), 60.0% (95% CI, 43.6%-74.4%), and 70.3% (95% CI, 54.2%-82.5%) of patients had no mineralocorticoid excess. Plasma adrenocorticotrophic hormone and urinary mineralocorticoid metabolites after 8 weeks were higher with prednisone 2.5 mg BID and 5 mg QD than 5 mg BID or dexamethasone. Urinary glucocorticoid metabolites may be higher in patients who did not meet the primary endpoint, regardless of glucocorticoid regimen. Total lean body mass decreased in the prednisone groups and total body fat increased in the prednisone 5 mg BID and dexamethasone groups. In the dexamethasone group, serum insulin and HOMA-IR increased and total bone mineral density decreased. In the prednisone 5 mg BID, 5 mg QD, 2.5 mg BID, and dexamethasone groups, respectively, median radiographic progression-free survival was 18.5, 15.3, 12.8, and 26.6 months. Conclusions and Relevance Abiraterone acetate with prednisone 5 mg BID or dexamethasone 0.5 mg QD met the prespecified threshold for the primary endpoint (95% CI excluded 50% mineralocorticoid excess); abiraterone acetate with prednisone 5 mg QD or 2.5 mg BID did not. Abiraterone acetate in combination with dexamethasone was particularly active but may be associated with adverse metabolic consequences.

Type: Article
Title: Glucocorticoid regimen options in combination with abiraterone acetate: an international, multicenter, randomized, open-label phase 2 study
Publisher version: https://jamanetwork.com/journals/jamaoncology
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10070288
Downloads since deposit
2Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item