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.
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.
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).Table: 824P
|Prior 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)||290||100||143|
|ALP median (U/l)||169||148||150|
|Time since diagnosis of prostate cancer, median (months)||81||53||64|
|Time between diagnosis of prostate cancer and bone metastases, median (months)||26||11||19|
|Time from diagnosis of bone metastases to Ra-223 treatment, median (months)||37||21||26|
|Prior 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)|
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.
Clinical trial identification
Legal entity responsible for the study
Medical writing support was provided by Rebecca Hopkins, BSc, of Scion, London UK, funded by Bayer.
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.