Universität zu Köln

Heidenreich, Axel, Gillessen, Silke ORCID: 0000-0001-5746-6555, Heinrich, Daniel, Keizman, Daniel, O'Sullivan, Joe M., Carles, Joan, Wirth, Manfred, Miller, Kurt, Reeves, John, Seger, Monica, Nilsson, Sten and Saad, Fred (2019). Radium-223 in asymptomatic patients with castration-resistant prostate cancer and bone metastases treated in an international early access program. BMC Cancer, 19. LONDON: BMC. ISSN 1471-2407

Full text not available from this repository.

Abstract

BackgroundRadium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking.MethodsThis was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6cm was allowed, visceral disease was excluded) received radium-223, 55kBq/kg intravenously, every 4weeks for up to 6cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline.ResultsSeven hundred eight patients received 1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3-4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease.ConclusionsUsing radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapies.Trial registrationThe study was registered with ClinicalTrials.gov, number NCT01618370 on June 13, 2012 and the European Union Clinical Trials Register, EudraCT number 2012-000075-16 on April 4, 2012.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heidenreich, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Gillessen, Silke UNSPECIFIED orcid.org/0000-0001-5746-6555 UNSPECIFIED Heinrich, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Keizman, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Sullivan, Joe M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Carles, Joan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED Reeves, John UNSPECIFIED UNSPECIFIED UNSPECIFIED Seger, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Nilsson, Sten UNSPECIFIED UNSPECIFIED UNSPECIFIED Saad, Fred UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-159469
DOI:	10.1186/s12885-018-5203-y
Journal or Publication Title:	BMC Cancer
Volume:	19
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2407
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SKELETAL METASTASES; ABIRATERONE ACETATE; INCREASED SURVIVAL; PLUS PREDNISONE; DOUBLE-BLIND; DICHLORIDE; PHASE-3; RA-223; ENZALUTAMIDE; CHEMOTHERAPY Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15946