F31 - External beam radiation therapy (EBRT) use and safety with radium-223 dichloride (Ra-223) in patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) from the ALSYMPCA trial

Abstract

Background: In ALSYMPCA, Ra-223, a first-in-class &agr;-emitter, improved overall survival and delayed time to first symptomatic skeletal event vs placebo (pbo). This post hoc analysis evaluated safety and efficacy of Ra-223 plus EBRT. Methods: Pts had symptomatic (recent EBRT for bone pain or any regular analgesic use) CRPC with ≥ 2 bone and no visceral mets; best standard of care; and prior docetaxel (pD) or were unfit for or declined docetaxel (no pD). Pts were stratified by pD use (yes/no), baseline total alkaline phosphatase level (tALP; < 220 U/L or ≥ 220 U/L), and current bisphosphonate (bp) use (yes/no) and randomized 2:1 to 6 Ra-223 injections (50 kBq/kg IV q 4 wk) or pbo. EBRT for bone pain was permitted within 12 weeks prior to randomization and during study. Baseline pain by prior EBRT, time to first on-study EBRT use for bone pain, and adverse events (AEs) by concomitant EBRT (cEBRT) were analyzed. Results: Pts with no prior EBRT had less pain at baseline; a WHO pain score ≤ 1 (no opioid use) was present in 46% (355/724) of pts with no prior EBRT vs 36% (53/147) of pts with prior EBRT. Ra-223 vs pbo significantly reduced EBRT use in the overall population (HR = 0.67, P = 0.001) and in pts with ≤ 20 bone mets (HR = 0.49, P < 0.001), current bp use (HR = 0.47, P = 0.004), tALP < 220 U/L (HR = 0.66, P = 0.008), and no pD (HR = 0.65, P = 0.038). At 6 months, the percentage of Ra-223 pts requiring EBRT was similar for prior and no prior EBRT subgroups (24% vs 20%), increasing at 12 months (38% vs 29%). cEBRT did not affect Ra-223 safety, and myelosuppression was low (Table). Conclusions: cEBRT did not adversely affect Ra-223 hematologic safety. Ra-223 significantly reduced risk of EBRT use. In Ra-223 pts, prior EBRT did not appear to affect later EBRT use. Clinical trial information: NCT00699751Table: F31cEBRTcEBRTNo cEBRTNo cEBRTPatients with AEs, n (%)Ra-223n = 227Pbon = 140Ra-223n = 373Pbon = 161HematologicAnemia77 (34)51 (36)110 (30)41 (26)Neutropenia14 (6)1 (1)16 (4)2 (1)Thrombocytopenia27 (12)8 (6)42 (11)9 (6)NonhematologicDiarrhea71 (31)26 (19)80 (21)19 (12)Nausea98 (43)61 (44)115 (31)43 (27)Vomiting56 (25)26 (19)55 (15)15 (9)Constipation54 (24)35 (25)54 (15)29 (18) Open table in a new tab