First interim results of the radium-223 (Ra-223) REASSURE observational study: Analysis of patient (Pt) characteristics and safety by use of abiraterone and/or enzalutamide (Abi/Enza)

Background: 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. Methods: 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. Results: 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%.Table807P Baseline characteristics and treatment completion by prior or concomitant*Prior = abi/enza stopped before starting Ra-223. Concomitant = any overlap with Ra-223. abi/enzaPrior – 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**Pts undergoing more than one imaging modality may be reported in multiple categories., n (%)<642 (26)123 (32)53 (37)112 (28)6–2081 (51)221 (58)86 (60)216 (54)>2039 (24)67 (17)27 (19)79 (20)Superscan14 (9)21 (5)5 (3)30 (8)ALP (U/L), median155115114134<140 U/L, n (%)58 (35)153 (37)54 (35)157 (37)≥140 U/L, n (%)73 (43)126 (30)51 (33)148 (34)PSA (ng/mL), median136434376LDH (U/L)***LDH was available for 209/583 patients., median327260291264Prior docetaxel or cabazitaxel, n (%)96 (57)100 (24)46 (30)150 (35)Completed 5 or 6 Ra-223 doses, n (%)87 (52)282 (68)106 (69)263 (61)* Prior = abi/enza stopped before starting Ra-223. Concomitant = any overlap with Ra-223.** Pts undergoing more than one imaging modality may be reported in multiple categories.*** LDH was available for 209/583 patients. Open table in a new tab Conclusions: 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: NCT02141438 Legal entity responsible for the study: Bayer Healthcare Funding: Bayer Healthcare Disclosure: 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.