Radium-223 in an International Early Access Program (EAP): Effects of Concomitant Medication on Overall Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Radium-223 in an International Early Access Program (EAP): Effects of Concomitant Medication on Overall Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC).
Presented by: Dr. Fred Saad. Professor and Chief of Urology and Director of GU Oncology at the University of Montreal Hospital Centers, in Montreal, Canada.
On behalf of my co-authors, it gives me great pleasure to present the Radium-223 International Early Access Program results: The Effects of Concomitant Medication on Overall Survival in Metastatic Castration Resistant Prostate Cancer.
The safety and efficacy data of radium-223 for an extended access program in which radium-223 was administered to patients enrolled from study sites in Canada, Europe, and Israel will be presented
As you know, radium-223 is the first α-particle emitting bone-targeting agent approved for use in CRPC patients with bone metastases.
The ALSYMPCA study treated metastatic castration resistant prostate cancer patients with symptomatic bone metastases using radium-223 and best standard of care, compared with placebo and best standard of care.
The results were published recently in the New England Journal of Medicine, showing significantly improved overall survival and time to first symptomatic skeletal event. The drug was very well tolerated, with minimal hematological toxicity.
The present study is a phase 3b, international, prospective, open-label, multicenter EAP. The eligibility criteria were very similar to the ALSYMPCA study, except that we allowed asymptomatic patients to be enrolled in this EAP.
Analysis of variables by descriptive statistics was done. The study was terminated on regulatory approval of radium-223, and there was a follow-up 30 days from the last patient treated.
The primary outcome of this analysis was safety and overall survival. There was also a planned exploratory analysis, including time to first symptomatic skeletal event; changes in total alkaline phosphatase activity and prostate specific antigen—or PSA—levels, from baseline. We also looked at time to ALP/PSA progression.
A post-hoc analysis that included overall survival in subgroups was based on concomitant medication at baseline that included abiraterone, enzalutamide, docetaxel, denosumab, and bisphosphonates. We also looked at overall survival based on baseline total ALP values; baseline ECOG performance status, and baseline pain.
A total of 839 patients were enrolled from 113 sites in 14 countries. [Of these] 149 patients did not meet inclusion criteria and were excluded; 696 patients were treated with at least one dose of radium-223; 291 patients discontinued early; and 473 patients entered active follow-up.
These are the details of patient disposition in the radium-223b study. Baseline patient characteristics in the EAP study were generally similar to those patients who were treated in the ALSYMPCA study, except that we allowed patients without pain to enter the [EAP] study and we looked at prior concurrent medical treatment.
In the EAP and ALSYMPCA study, the median number of RA-223 injections was similar, at 6. Fifty-eight percent of patients in the EAP and 63% of patients in ALSYMPCA received all 6 injections.
These are the baseline characteristics of the patients. As we notice, the median age of the patients was similar, at about 71 or 72. Eighty-one in the EAP versus 74% of patients [in the ALSYMPCA study] were over 65 years of age. The weight is similar, and approximately 88 percent of the patients had an ECOG performance status of 0 or 1.
In terms of other characteristics, time from prostate cancer diagnosis to study entry was approximately 5 years in both studies. The median time from bone metastases diagnosis to study entry was approximately 2 years in both [EAP and ALSYMPCA] studies. And the median PSAs at study entry in both studies were high, at around 140.
We also noticed that patients had elevated alkaline phosphatase, over 220: approximately 38% of patients in the EAP, and 43% in the ALSYMPCA study.
About 2/3 of patients [in both studies] had an ALP below 220.
The major difference between the EAP and the ALSYMPCA study was the fact that 21% of patients in the EAP came in to the study without any pain, allowing us to gather some information concerning this patient population.
In terms of study medication used prior to coming to the EAP study, 60% of EAP patients had prior use of docetaxel in EAP, [compared with] 57% of ALSYMPCA patients. Only 18% of patients in the EAP had used bisphosphonates—given the fact that it [denosumab] became available during the EAP and was unavailable during the ALSYMPCA study.
Also, abiraterone and enzalutamide were drugs that became available during the EAP program but were unavailable during the ALSYMPCA trial. This gave us the opportunity to look at how these drugs interact with radium-223