Ra-223 prolongs survival with a favorable safety profile in metastatic castration-resistant prostate cancer (mCRPC). The pivotal phase 3 ALSYMPCA trial had a relatively short 3-year follow-up and was conducted before availability of 2nd generation hormonal agents. The REASSURE study was designed to assess long-term safety (7 years follow-up) and conducted in an era when pts had access to other effective 1st line agents such as abi/enza.
REASSURE is a global, prospective, single-arm, observational study that enrolled pts with mCRPC with bone metastases planned to start Ra-223. Treatment decision was made independently before enrollment. We undertook a planned interim descriptive analysis of safety and drug completion based on prior or concomitant abi/enza use.
REASSURE enrolled 1106 pts in N. America and Europe from Sep 2014 to Sep 2016. The interim analysis included 583 pts who received ≥1 Ra-223 dose (Table; median 7 months observation). Prior abi/enza use was reported in 168 (29%) and concomitant in 153 (26%) pts. Treatment-related adverse events (TRAEs) occurred in 37%: prior abi/enza 45%, no prior abi/enza 34%; concomitant abi/enza 29%, no concomitant abi/enza 40%. TRAEs were most often gastrointestinal or hematological, with permanent discontinuation of Ra-223 in 6%: prior abi/enza 8%, no prior abi/enza 5%; concomitant abi/enza 5%, no concomitant abi/enza 7%. Serious TRAEs (mostly hematologic) occurred in 4.5% leading to permanent Ra-223 discontinuation in 1.5%.Table:
807P Baseline characteristics and treatment completion by prior or concomitant* abi/enza
|Prior – Yes (n = 168)||Prior – No (n = 415)||Concomitant – Yes (n = 153)||Concomitant – No (n = 430)|
|ECOG 0–1, n (%)||122 (73)||329 (79)||121 (79)||330 (77)|
|No. of metastases**, n (%)|
|20||39 (24)||67 (17)||27 (19)||79 (20)|
|Superscan||14 (9)||21 (5)||5 (3)||30 (8)|
|ALP (U/L), median||155||115||114||134|
Ra-223 has a good short-term safety profile when used in the routine clinical practice setting. Prior or concomitant abi/enza does not appear to increase TRAE incidence. Pts who had prior abi/enza had a lower rate of completing full Ra-223 dosing, perhaps reflecting poorer prognosis or more advanced disease as suggested by higher median PSA and LDH levels.
Clinical trial identification
Legal entity responsible for the study
L.C. Harshman: Advisory Board for Genentech, Dendron, Pfizer, Medivation/Astellas; Kew Research to the institution: Bayer, Sotio, BMS, Merck, Takeda, Dendrion/Valient, Janssen. C.N. Sternberg: Honoraria: Janssen, Sanofi, Astellas, Clovis, Bayer, Ferring. Research funding to institution: Roche/Genentech, Bayer, Sanofi, Janssen, Medivation, Sanofi Genzyme. S. Sundar: Advisory board of Bayer UK. D. Schrijvers: Studies in prostate cancer sponsored by Cougar, Janssen and Bayer. Advisory board of Janssen and Bayer. Speaker: Janssen and Bayer. M. Schostak: Advisory boards: Bayer, Sanofi, Janssen, Amgen and Astellas. Honorarium for scientific talks about mCRPC-Management from Bayer, Sanofi, Janssen, Amgen and Astellas. J. Sylvester: QLRAD, Royalties Theragenics, Consultant Augmenix, stock options Isoray, research grant. S. George: Grants and personal fees from BMS, Novartis, Pfizer, Bayer. Personal fees from Exelixis and AstraZeneca. Grants from Celldex, Agensys, and Merck. M. Tucci: Advisory Board for Bayer, Sanofi, Astellas, Janssen. P. Borrega: Head of Medical Oncology Service at Universitary Hospital San Pedro De Alcantara. (Cáceres, Spain), and IP on reassure study. Advisory board of Janssen, Bayer and Astellas Pharmaceutical Companies. K. Miller: Advisor to: Amgen, Astellas, AstraZeneca, Bayer, BMS, Ferring, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sotio, Takeda. All other authors have declared no conflicts of interest.