Radium-223 (Ra-223) therapy after abiraterone (Abi): Analysis of symptomatic skeletal events (SSEs) in an international early access program (iEAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

Background: Ra-223 phase 3 study (ALSYMPCA) was conducted before Abi became available. The Ra-223 iEAP study included Abi-treated pts. Here, we assessed SSEs, OS and bone health agent (BHA) use in Ra-223-treated pts who received Abi as a prior treatment. Methods: This open-label, single-arm trial enrolled pts with bone-predominant mCRPC (≥2 bone metastases [BM]). Pts who received prior anti-cancer therapies were included; use of BHAs (bisphosphonates and denosumab) was permitted before/during the study. Median follow-up was 7.5 mo. Baseline characteristics, SSEs, (EBRT, symptomatic pathological fractures, spinal cord compression or surgical intervention) and OS were analysed descriptively for pts who completed prior Abi therapy and Abi-naïve pts. Results: Of 708 mCRPC pts, 85% of prior Abi and 36% of Abi-naïve pts had previously received docetaxel (Table). During Ra-223 therapy, 14% and 17% of pts received concomitant bisphosphonates and 20% and 17% concomitant denosumab in the prior Abi and Abi-naïve groups, respectively. Median time since BM diagnosis and start of Ra-223 was 37 and 21 mo in the prior Abi and Abi-naïve pts, respectively. Median OS was 15.9 mo overall (11.2 mo for prior Abi and 17.1 mo for Abi-naïve pts). More pts had SSEs in the prior Abi (26%) than the Abi-naïve group (14%); proportions of treatment-emergent fractures were similar in both groups (4% and 3%, respectively), as was incidence of pathological bone fractures (5% for both). Conclusions: Pts in the prior Abi group had a longer time from diagnosis of BM to Ra-223 initiation. These pts seem more advanced, as reflected by higher median baseline PSA and more pts with prior docetaxel therapy. BHAs appear to be under-utilised in clinical practice in this pt population. A similar rate of pathological and non-pathological fractures was reported in Ra-223-treated pts regardless of prior use of Abi.Table: 824PPrior Abi (n = 223)Abi naïve (n = 321)Overall population (n = 708)ECOG: 0 and 1, n (%)195 (87)273 (85)618 (87)PSA, median (µg/l)290100143ALP median (U/l)169148150Time since diagnosis of prostate cancer, median (months)815364Time between diagnosis of prostate cancer and bone metastases, median (months)261119Time from diagnosis of bone metastases to Ra-223 treatment, median (months)372126Prior docetaxel, n (%)189 (85)117 (36)423 (60)Prior bisphosphonate, n (%)19 (9)13 (4)48 (7)Prior denosumab, n (%)6 (3)6 (2)14 (2)Concomitant bisphosphonates, n (%)30 (14)56 (17)122 (17)Concomitant denosumab, n (%)44 (20)53 (17)129 (18)Total Ra-223 injections, median (range)5.0 (1–6)6.0 (1–6)6.0 (1–6)OS, median (95% CI) (months)11.2 (9.7,13.5)17.1 (12.7, Not available)15.9 (13.4, Not available)Any SSE, n (%)58 (26)45 (14)145 (21)Treatment-emergent fracture, n (%)8 (4)11 (3)31 (4)Experienced pathological bone fracture, n (%)12 (5)15 (5)39 (6) Open table in a new tab Clinical trial identification: NCT01618370. Editorial acknowledgement: Medical writing support was provided by Rebecca Hopkins, BSc, of Scion, London UK, funded by Bayer. Legal entity responsible for the study: Bayer. Funding: Bayer. Disclosure: K. Miller: Honoraria, consultation fees: Amgen, Bayer, BMS, Ferring, Janssen, MSD, Novartis, Pfizer, Roche, Sotio, Takeda, Tolmar. D. Heinrich: Speaker, consultancy honoraries: Bayer, Janssen-Cilaq (Johnson & Johnson) J.M. O'Sullivan: Advisory boards, speaker's bureau: Bayer, Janssen, Sanofi. J. Carles: Consultant, scientific advisory board attendee: Johnson & Johnson, Astellas, Bayer, Amgen, Pfizer, BMS; Speaker's bureau: Bayer, Johnson & Johnson. M. Wirth: Advisory board:Vital GmbH. S. Nilsson: Advisory boards, remuneration: Bayer. L. Huang, J. Kalinovsky: Employee: Bayer Healthcare. A. Heidenreich: Honoraria, advisory board: Amgen, Astellas, Bayer, Ferring, Ipsen, Janssen, Pfizer, Takeda, Sanofi. F. Saad: Consultant, Research grants: Bayer, Amgen, Astellas, Jansssen, Sanofi, AstraZeneca.