ASCO GU 2018: First Interim Analysis Of REASSURE, An Observational Study To Assess The Safety Of Radium-223 In Men With Metastatic Castration-resistant Prostate Cancer

San Francisco, CA ( Radium-223 is a targeted alpha emitter that has previously been demonstrated to extend survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In the phase III ALSYMPCA study, in the final updated analysis of 921 patients, Ra-223 provided an overall survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of Ra-223 compared with placebo, and its safety profile was favorable at 3 years’ follow-up.1

As a follow-up, the REASSURE trial is a single-arm, prospective long-term observational study designed to evaluate long-term safety at 7 years’ follow up. In the study, patients with mCRPC with bone metastases were enrolled and planned to receive Ra-223. In this abstract, the authors provide the first interim analysis of 244 men treated in the United States – they have enrolled over 1106 men globally (421 United States), but only 244 were eligible for analysis. The primary aim was a descriptive analysis of safety and characteristics according to (1) prior or (2) concomitant abiraterone/enzalutamide (abi/enza) or (3) prior docetaxel/cabazitaxel (chemo) treatment in men who had received ≥1 Ra-223 dose; median follow up 8 months. Most men were ECOG 0-1.

20% had received prior chemotherapy (docetaxel/cabazitaxel), 19% had received prior abiraterone and/or enzalutamide, and 34% were treated concomitantly with abi or enza. 48% of men who had received prior abi/enza had also received prior chemotherapy; 44% of men who had received prior chemotherapy had also received prior abi/enza.
The median number of Ra-223 doses received was 6. Close to 70% completed 5-6 injections.

The key findings were that:
1. Prior abi/enza and/or chemo men had higher median baseline PSA and were less likely to complete 5-6 doses.
2. Subgroups had similar median ALP, LDH and Hb
3. Drug-related tx-emergent adverse events occurred in 71 pts (29%) and serious AEs in 9 (3.7%). Most common AEs were diarrhea (9%), fatigue (8%) and anemia (7%). Drug-related serious AE’s occurred in 4% of patients.
4. AE incidence was numerically higher in pts who received prior chemo and/or prior abi/enza
5. In the updated safety analysis, 51/244 (21%) had a symptomatic skeletal related event (SSE)

Based on this interim analysis, there are no new safety concerns and most men complete 5-6 Ra-223 doses in routine US clinical practice. Men who received prior abi/enza or prior chemo had lower Ra-223 treatment completion and higher AE incidence – this is likely due to greater disease burden, as they had a higher median baseline PSA.

Speaker: Lauren Christine Harshman

Co-Authors: AA. Oliver Sartor, Timothy Richardson, John Sylvester, Daniel Y. Song, Constantine Mantz, Robert K. Brookland, Mark Perlmutter, Robert Given, Jan Kalinovsky, Svetlana Babajanyan, Yoriko De Sanctis, Celestia S. Higano

Institution(s): Dana-Farber Cancer Institute, Boston, MA; Tulane University School of Medicine, New Orleans, LA; Wichita Urology, Wichita, KS; 21st Century Oncology, Lakewood Ranch, FL; Johns Hopkins School of Medicine, Baltimore, MD; 21st Century Oncology, Fort Myers, FL; Chesapeake Urology, Towson, MD; Jersey Shore Medical Center, Neptune, NJ; Urology of Virginia, Virginia Beach, VA; Bayer HealthCare Pharmaceuticals Inc., Basel, Switzerland; Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ; University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

1. Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzén L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland ØS, Sartor O; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23. doi: 10.1056/NEJMoa1213755.

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