ORLANDO, FL, USA (UroToday.com) - Radium-223 is an FDA approved alpha-emitter shown to prolong survival in castrate-resistant prostate cancer (CRPC) with symptomatic bone metastasis (ALSYMPCA study). In ALSYMPCA study, radium-223 compared to placebo was associated with significantly improved overall survival (p < 0.001), delayed time to first symptomatic skeletal event (p < 0.001), time to first EBRT (p < 0.001), prolonged time to alkaline phosphatase (ALP), and PSA progression (p < 0.001).
The group here reports from the prospectively reported Expanded Access Program (EAP) on monitoring acute and long-term safety of Ra-223. The EAP program was initiated as a prospective, interventional, open-label, multicenter study designed to provide radium-223 to CRPC patients with symptomatic bone metastasis, and to assess acute and long-term safety.
Primary end-points of the EAP were ECOG PS, symptomatic skeletal-related events (SSE), treatment-emergent adverse events (TEAEs), and routine laboratory tests, including PSA. The secondary end-points were overall survival, SSE rates, changes in total ALP (tALP)/PSA responses, time to tALP normalization, and to tALP and PSA progression.
One hundred and eighty-four patients entered treatment under EAP. Baseline characteristics were similar as seen in ALSYMPCA study. However, as compared to ALSYMPCA cohort who had prior docetaxel, EAP group also had patients who underwent prior docetaxel, carbazitaxel, abiraterone, and enzalutamide. Greater cohort of patients in the EAP group had radiotherapy to prostate or prior prostatectomy. Sixty-seven percent had total ALP < 220 U/L and 47% mild-to-moderate pain. 81/184 (44%) received all 6 injections; 26 (14%) had dose interruptions/delay, 18 due to AEs. Median OS was 17 months. TEAEs occurring at ≥ 10% were anemia, fatigue, diarrhea, and nausea. The most common Grade 3/4 hematologic TEAE was anemia (11%). The majority of patients had no change in ECOG PS. Nineteen (10%) patients had an SSE. Thirty-three percent of patients had a ≥ 30% confirmed ALP decline from baseline and 16% had a ≥ 50% decline. Median time to PSA progression was 4 months and 6% had a confirmed PSA response.
The authors concluded that RA-223 was well tolerated in the EAP despite these patients being heavily pretreated. There were no new safety concerns, and positive effect was seen in efficacy parameters (PSA response, ALP decline, OS).
Presented by Nicholas J. Vogelzang, Daniel Celestino Fernandez, Michael J. Morris, Andrei Iagaru, Alan Brown, Fabio Almeida, Christopher Sweeney, Matthew Raymond Smith, Adam Dicker, Yu-Ning Wong, Neal D. Shore, Keith Bangerter, Oana Petrenciuc, and A. Oliver Sartor at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA
Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Moffitt Cancer Center, Tampa, FL; Memorial Sloan Kettering Cancer Center, New York, NY; Stanford University, Stanford, CA; 21st Century Oncology, Fort Myers, FL; Arizona Molecular Imaging Center, Phoenix, AZ; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA; Thomas Jefferson University, Philadelphia, PA; Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA; Carolina Urologic Research Center, Myrtle Beach, SC; Bayer HealthCare, Whippany, NJ; Tulane Cancer Center, New Orleans, LA
Reported by Mohammed Haseebuddin, MD, medical writer for UroToday.com