Bone metastases are a major source of morbidity in metastatic castration-resistant prostate cancer, contributing to pain, functional decline, skeletal-related events, and impaired quality of life.
Radium-223 is an established radiopharmaceutical treatment for mCRPC with symptomatic bone metastases. In the COMRADE trial, investigators evaluated whether adding the PARP inhibitor olaparib to radium-223 could improve outcomes in patients with mCRPC and bone metastases. The previously reported primary analysis showed improved radiographic progression-free survival with the combination compared with radium-223 alone.
A new patient-reported outcome analysis from COMRADE assessed whether the addition of olaparib affected quality of life or pain.
The article, titled “Patient-reported outcomes in castration-resistant prostate cancer with bone metastases treated with radium-223 with or without olaparib,” was first published in Cancer on June 19, 2026.
Authors: Rana R. McKay, Wanling Xie, Archana Ajmera, Arlene Araneta, Edmund Folefac, Arif Hussain, Christos E. Kyriakopoulos, Adam Olson, Mamta Parikh, Rahul Parikh, Biren Saraiya, and Geoffrey I. Shapiro.
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About the COMRADE Trial
COMRADE was a multicenter, randomized, open-label, phase 2 trial conducted across academic centers in the United States through the National Cancer Institute Experimental Therapeutics Clinical Trials Network.
The study included patients with histologically or cytologically confirmed prostate cancer, progressive castration-resistant disease, at least 2 bone metastases on imaging, and no visceral metastases. Prior therapy for mCRPC was allowed, but patients could not have received prior PARP inhibitors or radium-223.
All patients received a bisphosphonate or denosumab unless medically contraindicated. Eligible patients also had an ECOG performance status of 0 or 1 and adequate bone marrow and organ function.
Patients were randomized 1:1 to receive:
- Olaparib 200 mg orally twice daily continuously plus radium-223 55 kBq/kg intravenously every 4 weeks for up to 6 cycles
or
- Radium-223 alone at the same dose and schedule.
Randomization was stratified by prior docetaxel exposure and extent of bone disease. Patients assigned to radium-223 alone were permitted to cross over to olaparib at radiographic progression.
Previous COMRADE Efficacy Results
The primary efficacy and safety results of COMRADE were previously published in the Journal of Clinical Oncology. In that report, 120 patients were randomized. Most patients had received prior androgen receptor pathway inhibitor therapy, 52% had received docetaxel, 47% had more than 20 bone metastases, and 90% received bone-protecting agents.
Olaparib plus radium-223 significantly improved investigator-assessed radiographic progression-free survival compared with radium-223 alone. Median rPFS was 8.9 months with the combination and 4.7 months with radium-223 alone, with a hazard ratio of 0.50.
The rPFS benefit was most pronounced among patients without prior docetaxel and among those with 20 or fewer bone metastases. The 1-year cumulative incidence of symptomatic skeletal-related events was lower with olaparib plus radium-223, while median overall survival was similar between arms.
Grade 3 or higher treatment-related adverse events occurred more often with the combination, mainly hematologic events, including lymphopenia, anemia, and thrombocytopenia. The new Cancer publication builds on these efficacy and safety findings by focusing on patient-reported quality of life and pain outcomes.
Patient-Reported Outcome Analysis
Patient-reported outcomes were assessed using 2 validated tools: the Functional Assessment of Cancer Therapy–Prostate and the Brief Pain Inventory Short Form. FACT-P was used to evaluate prostate cancer–related quality of life. Higher FACT-P scores indicate better quality of life.
BPI-SF was used to assess pain severity and pain interference. Higher BPI scores indicate worse pain or greater pain interference. Assessments were performed at baseline, every 12 weeks, and at the end-of-study visit. Because questionnaire completion declined after 24 weeks, the main PRO analysis focused on the first 24 weeks after treatment initiation.
Clinically meaningful FACT-P change was defined as a 10-point or greater change in total score. For BPI pain severity and pain interference, clinically meaningful worsening was defined as a 30% or 2-point or greater increase from baseline.
Evaluable Population
In COMRADE, 120 patients were randomized and 114 received allocated treatment. Of the 114 treated patients, 74 were included in the PRO-evaluable population. This included 40 patients in the olaparib plus radium-223 arm and 34 patients in the radium-223 alone arm.
Baseline characteristics were generally balanced between groups. Median age was 70 years in the combination arm and 72 years in the radium-223 alone arm. ECOG performance status was 1 in 60% and 62% of patients, respectively.
Prior docetaxel had been received by 55% of patients in the combination arm and 50% in the radium-223 alone arm. More than 20 bone metastases were present in 45% and 47% of patients, respectively. Baseline pain medication use was numerically higher in the radium-223 alone arm.
Quality-of-Life Results
There were no significant differences in FACT-P total score change between treatment arms at Week 12 or Week 24. At Week 12, the least-squares mean change from baseline in FACT-P total score was −5.09 with olaparib plus radium-223 and −0.23 with radium-223 alone. The between-arm difference was −4.87, with a 95% confidence interval of −13.4 to 3.62.
At Week 24, the least-squares mean change was −1.41 with olaparib plus radium-223 and −3.20 with radium-223 alone. The between-arm difference was 1.79, with a 95% confidence interval of −8.28 to 11.9.
The numerical decline seen at Week 12 in the combination arm was below the 10-point threshold for clinically meaningful FACT-P worsening and was not sustained at Week 24. By 24 weeks, clinically meaningful FACT-P worsening occurred in 40% of patients treated with olaparib plus radium-223 and 42% of patients treated with radium-223 alone. Clinically meaningful improvement occurred in 23% and 32%, respectively.
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Pain Results
Pain severity did not differ significantly between arms at Week 12 or Week 24. At Week 12, the least-squares mean change in BPI-SF pain severity was 0.11 with olaparib plus radium-223 and −0.33 with radium-223 alone. The between-arm difference was 0.44, with a 95% confidence interval of −0.44 to 1.33.
At Week 24, the least-squares mean change was 0.24 with olaparib plus radium-223 and 0.44 with radium-223 alone. The between-arm difference was −0.20, with a 95% confidence interval of −1.32 to 0.93. For BPI pain interference, radium-223 alone showed greater improvement at Week 12. The between-arm difference was 1.09, with a 95% confidence interval of 0.14 to 2.05. However, this difference was not sustained at Week 24.
By 24 weeks, clinically meaningful worsening in pain severity occurred in 31% of patients treated with olaparib plus radium-223 and 30% treated with radium-223 alone. Clinically meaningful worsening in pain interference occurred in 33% and 34%, respectively.
Safety Context
The PRO findings are notable because the combination arm had a higher rate of grade 3 or higher treatment-related adverse events in the primary analysis, mainly hematologic events. Grade 3 or higher treatment-related adverse events occurred in 56% of patients treated with olaparib plus radium-223 and 33% treated with radium-223 alone.
Despite the higher rate of grade 3 or higher treatment-related adverse events in the combination arm, the addition of olaparib did not lead to significant or clinically meaningful worsening in patient-reported quality of life or pain through 24 weeks.
Limitations
The PRO analysis was exploratory, and the study was not powered for patient-reported outcome comparisons. No adjustment for multiplicity was applied. The sample size was modest, and confidence intervals around between-arm differences were wide. Questionnaire completion declined over time, and reasons for noncompletion were not systematically captured. The open-label design may also have influenced patient-reported responses. In addition, crossover from radium-223 alone to olaparib required truncation of PRO data after crossover.
Takeaway
In this PRO analysis of the randomized phase 2 COMRADE trial, adding olaparib to radium-223 did not significantly worsen patient-reported quality of life or pain compared with radium-223 alone in patients with metastatic castration-resistant prostate cancer and bone metastases.
Together with the previously reported radiographic progression-free survival benefit, these findings support the tolerability of olaparib plus radium-223 from the patient perspective.