Radium-223, Alone or With Novel Hormonal Agents, Is Well-Tolerated by Men with Symptomatic Chemotherapy-naïve mCRPC

Researchers at Cleveland Clinic and Tulane University reported the results of a study evaluating the contemporary use of Radium-223 given alone or in combination with novel hormonal therapeutics to men with symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).

In general, the researchers found that Ra-223 treatment was well-tolerated, and that the addition of either oral abiraterone acetate (AA) or enzalutamide (ENZ) did not impact the previously reported safety profile for Ra-223. Cleveland Clinic hematology/oncology Fellow Hamid Emamekhoo, MD, says the results suggest that when using Ra-223, the novel agents abiraterone and enzalutamide could be considered best standard of care and given concomitantly with the radiopharmaceutical.

Dr. Emamekhoo presented a general poster session on the study at the American Society of Clinical Oncology’s 2015 Genitourinary Cancers Symposium.

The retrospective study’s goal was to determine the efficacy and safety of Ra-223 given in a contemporary setting and to determine the feasibility, efficacy and safety profile of Ra-223 given alone or in combination with AA or ENZ to men with symptomatic chemotherapy-naïve mCRPC.

Background

Ra-223 is a calcium mimetic α-emitter that selectively targets osteoblastic metastatic lesions. Treatment with Ra-223 has been shown to delay symptomatic skeletal-related events (SREs) and to improve overall survival in men with symptomatic mCRPC. Concerns about the efficacy and safety of Ra-223 in the pre-chemotherapy space, given alone or in combination with AA or ENZ, have been raised.

Study Methods

The researchers conducted a retrospective study of 51 chemo-naïve mCRPC patients with bone metastases who received Ra-223 treatment. Twenty-three patients received Ra-223 alone, and 22 patients received concomitant AA or ENZ therapy. To date, the median number of Ra-223 cycles received is five, with 39 percent of patients receiving all six cycles. The researchers recorded pre- and post-Ra-223 treatment hemoglobin, platelet counts and absolute neutrophil counts, and measured Grade 3/4 adverse events based on the Common Terminology Criteria for Adverse Events. They analyzed prostate specific antigen (PSA) decline, radiographic progression-free survival and safety data.

Study Results

“Although prospective studies would be required to confirm our initial data, concomitant use of Ra-223 with AA or ENZ did not increase treatment-related side effects in our patients,” Dr. Emamekhoo says. “The drugs were very well-tolerated without significant adverse events, even in patients who were not eligible for systemic palliative chemotherapy.”

There was no statistical difference in toxicity between patients who received concurrent treatment with AA or ENZ and those treated with Ra-223 alone. At the time of the analysis, 14 percent of patients were still on treatment and 39 percent had completed all six cycles. Thirty-five percent of patients discontinued Ra-223 treatment due to progression of disease and 8 percent discontinued due to treatment-related adverse events. A large majority of patients (81 percent) had PSA progression, and 42 percent of patients died. Patients with normal baseline hemoglobin levels and those who received concomitant AA tended to stay PSA progression-free longer and had better overall survival.

Future Research

Dr. Emamekhoo recommends more research to evaluate the impact of the combination of Ra-223 and these novel oral agents on symptomatic skeletal events/SREs and on overall survival. “Our study had a small sample size and was retrospective in nature,” he says. “We need to conduct larger studies with longer follow-up to see if the reduced SREs seen in the initial trials that led to FDA approval of AA and ENZ for the treatment of CRPC would be further improved when those therapies are used concomitantly with Ra-223, and to see if concomitant treatment would improve overall survival. We also need to study the sequence of utilization of these different treatment lines.”