When the Ra-223 phase 3 clinical trial (ALSYMPCA) was conducted, Abi was not available; REASSURE is a prospective, observational clinical study of Ra-223 in pts with mCRPC with a 7-year follow-up (NCT02141438). Pts could have had anti-hormonal agents, such as Abi, prior to receiving Ra-223. The objective of this interim review was to evaluate the fractures and skeletal-related events (SREs) based on prior Abi and the use of BHAs, denosumab and bisphosphonates.
Descriptive statistics were generated for baseline characteristics, fractures, SREs and overall survival (OS) by BHA use in pts who had completed Abi treatment prior to receiving Ra-223 (prior Abi) or who had no prior Abi (Abi-naïve). An SRE was defined as any skeletal-related adverse event or any radiotherapy to bone.
As of Nov 2017, 1439 pts were enrolled, with a median follow-up time of 9.1 months. 708 (49%) pts had received BHAs at baseline, and BHAs were given concomitantly with Ra-223 in 553 (38%) pts. 430 (30%) pts received prior Abi, and Ra-223 was given as second line in 37% (157/430) of those pts; 705 (49%) pts were considered Abi-naïve. For the prior Abi group, median time of exposure to Abi was 11 months. In the prior Abi group SREs occurred in 17% and 22% of pts, with and without BHAs, respectively. In the Abi-naïve group, 16% of pts had SREs regardless of BHA use. Fractures were reported in 7/430 pts (1.6%) in the prior Abi group. In the Abi-naïve group fractures were reported in 2/311 (1%) and 8/394 (2%) pts with and without BHAs, respectively (Table).Table: 826P
|Abi-naïve pts (n = 705)||Prior Abi pts (n = 430)||Overall cohort (n = 1439)|
|With BHAs (n = 311)||Without BHAs (n = 394)||With BHAs (n = 216)||Without BHAs (n = 214)||With BHAs (n = 708)||Without BHAs (n = 731)|
|Time from CRPC to Ra-223 initiation, median months (range)||6 (0–134)||10 (0–109)||23 (0–80)||23 (0–117)||12 (0–147)||13 (0–117)|
|PSA, median ng/mL (Q1, Q3)||49 (11, 160)||46 (15, 161)||114 (31, 331)||121 (30, 311)||60 (14, 212)||59 (19, 201)|
|Prior docetaxel,n (%)||95 (31)||106 (27)||122 (57)||120 (56)||273 (39)||269 (37)|
|≥1 SRE, n (%)||49 (16)||62 (16)||36 (17)||46 (22)||116 (16)||129 (18)|
|≥1 fracture, n (%)||2 (1)||8 (2)||2 (1)||5 (2)||7 (1)||17 (2)|
|5–6 Ra-223 injections, n (%)||199 (64)||252 (64)||128 (59)||128 (60)||480 (68)||465 (64)|
|OS from initiation of Ra-223, median months (95% CI)||15.5 (13.1, 16.6)||11.1 (10.2, 11.8)||14.8 (13.5, 16.0)|
BHAs were under-utilised in this study despite several guidelines and recommendations. The rate of fracture was the same in those who were Abi-naïve compared with those who received Abi prior to Ra-223. Pts with prior Abi had a shorter OS; these pts received Ra-223 at a later time during their disease course, as reflected by a longer time from CRPC to Ra-223 initiation.
Clinical trial identification
Legal entity responsible for the study
Medical writing support was provided by Michael Sheldon of Scion, London UK, funded by Bayer.
C.N. Sternberg: Honoraria or consulting fees: Bayer, Sanofi, Pfizer, Janssen, Astellas, Clovis, Novartis. B. Tombal: Investigator, paid advisor: Bayer, Astellas, Janssen, Sanofi. K. Miller: Honoraria, consultation fees: Amgen, Bayer, BMS, Ferring, Janssen, MSD, Novartis, Pfizer, Roche, Sotio, Takeda, Tolmar. F. Saad: Consultant, research grants: Bayer, Amgen, Astellas, Jansssen, Sanofi, AstraZeneca. O. Sartor: Consultant, investigator: Bayer. J. Bellmunt: Advisory role: Genentech, MSD, Pfizer, GSK, BMS, Pierre-Fabre, Sanofi Aventis, Astellas, OncoGenx, Janssen; Lecture fees: Pfizer, MSD, GSK, Novartis, Pierre-Fabre, Astellas; Research funding: Takeda, Pfizer, Novartis, Sanofi Aventis. S. Dizdarevic: Support, travel expenses, registration costs for occasional conference, advisory role: Bayer. L.C. Harshman: Advisory: Bayer, Genentech, Dendreon, Pfizer, Medivation/Astellas, Kew Group, Theragene, Corvus, Merck, Exelixis, Novartis; Research to institution: Bayer, Sotio, Bristol-Myers Squib, Merck, Takeda, Dendreon/Valient and Janssen. J. Logue: Honoraria: Bayer. T. Richardson: Speaker, peer advisor: Bayer (Xofigo); Speaker: Janssen (Erleada), Astellas (Myrbetriq). D. Bottomley: Honoraria, travel/subsistence grants: Bayer, Janssen, AccelyonBT. M. Schostak: Advisor: Bayer. I. Bayh: Employee, consultant: Fresenius Medical Care; Stocks: Fresenius Medical Care Deutschland GmBH. J. Kalinovsky: Employee: Bayer. C. Higano: Advisory boards: Astellas, Bayer, Blue Earth Diagnostics, Ferring, Janssen, Myriad, Tolmar; Sponsored research: Aragon, Astellas, AstraZeneca, Dendreon, Genentech, Medivation, Emergent, Bayer, Pfizer, Hoffman La Roche: Employment: Spouse employed in leadership position: CTI Biopharma. All other authors have declared no conflicts of interest.