Ra-223 pivotal phase 3 trial was conducted prior to Abi and Enza becoming available. Here, we analysed registry data to determine clinical outcomes with Ra-223 therapy in pts previously treated with Abi or Enza in a RW setting.
This was a retrospective study of data from the Flatiron prostate cancer registry, providing electronic health records from >245 US cancer clinics. Data were collected from 01/01/2013–30/06/2017. Ra-223-treated mCRPC pts were included; prior to receiving Ra-223, pts completed Abi/Enza/both. Prior Abi and prior Enza groups excluded pts with concomitant/concurrent Abi or Enza. Baseline was defined as the index date at start of Ra-223 therapy. Pts were followed until death or study end. Descriptive analysis was performed for baseline characteristics, prior Abi or Enza therapy, skeletal-related events (SREs) and OS (Kaplan–Meier method).
Among 625 Ra-223-treated pts, 29.9% (n = 187) and 26.2% (n = 164) completed prior Abi or Enza treatment, respectively (Table). At baseline, SREs were documented in 50% (314/625) of pts (48% [89/187] in prior Abi and 53% [87/164] in prior Enza pts). During/following Ra-223 therapy, SREs were reported at a similar rate in prior Abi (21% [39/185]) and prior Enza pts (20% [33/163]). Pathological fractures were reported in 10% (61/623) of pts (7% [13/185] and 6% [10/163] in prior Abi and prior Enza pts, respectively). Median (95% CI) OS was 15.2 (13.2–16.3) months in all pts (10.5 [8.6–12.3] for prior Abi and 9.8 [7.8–13.2] for prior Enza pts).Table: 827P
|Ra-223 pts with prior Abi (n = 187)||Ra-223 pts with prior Enza (n = 164)||All Ra-223 pts (n = 625)|
|Age, median (years)||75||75||73|
|ECOG 0–1, n (%)||84 (45.0)||73 (44.5)||260 (41.6)|
|ALP (U/L), median||111||113||108|
|PSA (μg/L), median||67||53||38|
|LDH (U/L), median||204||207||196|
|Time from castration resistance to baseline, median (months)||18||16||11|
|Pts with prior SREs, n (%)||89 (47.6)||87 (53.0)||314 (50.2)|
|Duration of prior therapy (months)|
|Abi, median (range)||5.8 (0.0–46.9)||Not applicable||Not calculated|
|Enza, median (range)||Not applicable||4.8 (0.0–49.0)||Not calculated|
|Clinical outcomes with Ra-223 therapy|
|Follow-up time, median (months)||7||7||9|
|Ra-223 doses, median (range)||4 (1–6)||4 (1–6)||4 (1–6)|
|Pts with SREs, n (%)||39 (21)||33 (20)||168 (27)|
|Pts with pathological fractures, n (%)||13 (7)||10 (6)||61 (10)|
|Median time from castration resistance to death (months)||29||26||26|
|OS, median (95% CI) (months)||10.5 (8.6, 12.3)||9.8 (7.8, 13.2)||15.2 (13.2, 16.3)|
In this retrospective RW study of 4 yr clinical practice, a high proportion of pts had SREs prior to start of Ra-223. Sequential use of Ra-223 after Abi or Enza does not negatively affect bone-related safety outcomes when compared with the overall cohort. Ra-223 is a feasible treatment option after Abi or Enza.
Clinical trial identification
Legal entity responsible for the study
Medical writing support was provided by Samantha Kew, BSc, of Scion, London UK, funded by Bayer.
C.S. Higano: Advisory boards: Astellas, Bayer, Blue Earth Diagnostics, Ferring, Janssen, Myriad, Tolmar; Sponsored research: Aragon, Astellas, AstraZeneca, Dendreon, Genentech, Medivation, Emergent, Bayer, Pfizer, Hofman Laroche; Employment: Spouse employed in leadership position: CTI Biopharma. 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 and AstraZeneca. O. Sartor: Consultant, investigator: Bayer. K. TangiralaX. Jiao, J. Kalinovsky: Employee: Bayer Healthcare. C.N. Sternberg: Bayer, Sanofi, Pfizer, Janssen, Astellas, Clovis, AstraZeneca.