769P - 1.5-Year Posttreatment Follow-Up of Radium-223 Dichloride (Ra-223) Safety in Patients (Pts) with Castration-Resistant Prostate Cancer (Crpc) and Symptomatic Bone Metastases from Alsympca: Characterization of Hematologic Safety Profiles

Abstract

ABSTRACT Aim: In ALSYMPCA, the first-in-class alpha-emitter Ra-223 had a highly favorable safety profile and was well tolerated (Parker et al. NEJM 2013). Safety monitoring of Ra-223 is essential for a complete safety profile. Reported here are safety results of a post hoc analysis from an interim review of ∼1.5 years after the last pt's last injection. Methods: Pts were to enter designated follow-up starting 4 weeks after their last injection until 3 years after first injection. Pts were to be evaluated at 9 follow-up visits. Only adverse events (AEs) considered treatment (tx) related were reported. Long-term safety was assessed by specific diseases (acute myelogenous leukemia [AML], myelodysplastic syndrome [MDS], aplastic anemia [AA], new primary bone cancer, and new primary cancer in other organs). Results: Of 921 pts (Ra-223, n = 614; placebo [pbo], n = 307), 574 entered follow-up (Ra-223, n = 406; pbo, n = 168). Median follow-up time was 10.4 months with Ra-223 and 7.6 months with pbo. In the safety population, 25/404 (6%) Ra-223 pts and 8/167 (5%) pbo pts had 37 tx-related AEs. Overall, myelosuppression incidence was ≤ 3%. Leukopenia, neutropenia, or thrombocytopenia occurred in 7 Ra-223 pts (Table). As shown, 6 had prior docetaxel and 4 had extent of disease (EOD) grade 3; 2 completed long-term follow-up, 4 did not due to death or disease progression. Grade 3/4 anemia occurred in 5 Ra-223 pts and 1 pbo pt; their data will be presented. To date, no pts had AML, MDS, or primary bone cancer; 1 Ra-223 pt had AA; 5 pts had primary cancer in other organs (Ra-223, n = 2; pbo, n = 3). Pt Data and Characteristics for the 7 Ra-223 Pts With Either Leukopenia, Neutropenia, or Thrombocytopenia Parameter Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Hematologic AE Thrombo- cytopenia (grade 1) Leukopenia/ Neutropenia (grade 3) Leukopenia (grade 4) Thrombo- cytopenia (grade 2) Thrombo- cytopenia (grade 2) Neutropenia (grade 3) Thrombo- cytopenia (grade 1) Age 65 68 74 61 64 79 72 Baseline ECOG score: 0 = fully active; 1 = physical strenuous activity restricted 1 1 1 0 1 0 1 WHO ladder for cancer pain:1 = mild, no opioids; 2 = moderate, occasional opioids; 3 = severe, regular daily opioids 3 1 1 1 3 3 2 EOD (grades): 1 = 20 mets 3 3 3 2 1 1 3 Prior docetaxel yes yes yes yes yes no yes Concomitant cancer tx Luteinizing hormone– releasing hormone analogue (LHRHa) Zoledronic acid LHRHa Zoledronic acid LHRHa Prednisolone LHRHa LHRHa Dexamethasone Diethylstilbestrol Zoledronic acid LHRHa Zoledronic acid LHRHa Prednisone No. of Ra-223 inj received 6 6 5 6 6 5 6 Status of follow-up Completed Withdrew (pt request) Withdrew (death) Completed Withdrew (death) Withdrew (death) Withdrew (disease progression) Conclusions: Long-term follow-up of ∼1.5 years after last pt's last injection showed no major hematologic safety issues. Hematologic toxicity appeared to be associated with prior docetaxel and EOD grade 3, and did not affect number of Ra-223 injections received. Disclosure: C. Parker: has had a consultant or advisory relationship with Algeta, Bayer, and BNIT, and has received honoraria from Amgen, Astellas, Bayer, Janssen, Sanofi-Aventis, and Takeda; N. Vogelzang: has had a consultant or advisory relationship with Bayer, Algeta, Janssen, and Medivation, and has received honoraria from Bayer.v; . Sartor: has had a consultant or advisory relationship with and has received research funding from Algeta and Bayer; R.E. Coleman: has served as a consultant for Bayer, has received honoraria from Bayer and Amgen, and has provided expert testimony for Novartis; I. Skjorestad: is employed by and has an ownership interest in Algeta ASA (Bayer); A. Aksnes: is employed by Algeta ASA (Bayer); M. Wahba: is employed by Bayer HealthCare; S. Nilsson: has had a consultant or advisory relationship with Algeta and has received remuneration from Bayer for travel costs and accommodations for study and writing meetings. All other authors have declared no conflicts of interest.