The addition of olaparib (Lynparza) to radium‐223 (Xofigo) was not associated with significant detriment to patient-reported outcomes (PROs) or pain in patients with metastatic castration‐resistant prostate cancer (mCRPC) with bone metastases, according to data from the PRO analysis of the phase 2 COMRADE trial (NCT03317391) published in Cancer.1
Findings from the analysis revealed that no significant differences in Functional Assessment of Cancer Therapy–Prostate (FACT‐P) total score change were observed at week 12 (−4.87; 95% CI, −13.4 to 3.62) or week 24 (1.79; 95% CI, −8.28 to 11.9) between the olaparib plus radium‐223 arm compared with the radium‐223 alone arm. Additionally, no significant difference in Brief Pain Inventory (BPI) pain severity was observed at week 12 or 24, at 0.44 (95% CI, −0.44 to 1.33) and −0.20 (95% CI, −1.32 to -0.93), respectively.
“Our findings are consistent with the broader body of evidence on PARP inhibitor effects on PROs in mCRPC,” Rana R. McKay, MD, a medical oncologist and professor in the Department of Medicine and Department of Urology at UC San Diego School of Medicine, and her coauthors wrote in the publication. “The COMRADE PRO data add to this evidence by extending these observations to a radiopharmaceutical combination context not previously evaluated for PRO impact.”
Prior data from COMRADE demonstrated that the addition of olaparib to radium‐223 led to a significant radiographic progression-free survival (rPFS) benefit vs radium‐223 alone (1-sided 90% CI, 0.35-0.70; 1-sided P = .0042).2 The median rPFS values in the investigational (n = 61) and control arms (n = 59) were 8.9 months (95% CI, 5.4-13.7) and 4.7 months (95% CI, 3.2-6.0), respectively.
COMRADE Trial PRO Analysis: Key Takeaways
- Adding olaparib to radium-223 did not significantly worsen patient-reported outcomes or pain vs radium-223 alone, with no meaningful differences in FACT-P scores or pain severity at weeks 12 or 24.
- These PRO findings complement previously reported improvements in radiographic progression-free survival, with olaparib plus radium-223 achieving a median rPFS of 8.9 months vs 4.7 months for radium-223 alone in the phase 2 COMRADE trial.
- Exploratory analyses showed similar rates of clinically meaningful pain worsening between treatment arms through 24 weeks, supporting the tolerability and clinical viability of the combination in patients with mCRPC and bone metastases.
How was COMRADE designed and how were the PRO analyses conducted?
COMRADE was a multicenter, randomized, open‐label study that enrolled patients with histologically or cytologically confirmed prostate cancer with progressive castration‐resistant disease per Prostate Cancer Working Group 3 criteria.1 Patients were also required to have at least 2 bone metastases per radiographic imaging and no visceral metastases, an ECOG performance status of 0 or 1, and adequate bone marrow and organ function. Prior therapy for mCRPC was allowed; however, patients could not have received prior PARP inhibitors or radium‐223.
Eligible patients were randomly assigned 1:1 to receive oral olaparib at 200 mg twice daily continuously in combination with intravenous radium‐223 at 55 kBq/kg every 4 weeks for up to 6 cycles or radium‐223 monotherapy. Patients were stratified by prior docetaxel exposure (yes vs no) and extent of bone disease (≤20 vs >20 bone lesions). Crossover to the investigational arm was permitted at the time of radiographic disease progression.
PROs were assessed using the FACT‐P and BPI Short Form. Questionnaires were administered on day 1 of cycle 1, every 12 weeks (±7 days), and at the end‐of‐study visit.
At baseline, patients in the combination (n = 40) and monotherapy (n = 34) arms were a median age of 70 years (IQR, 62-77) and 72 years (IQR, 66-76), respectively. Most patients in both arms were White (87.5% vs 91.2%), not Hispanic or Latino (95.0% vs 94.1%), had a Gleason score of 8 to 10 at initial diagnosis (50.0% vs 70.6%), and an ECOG performance status of 1 (60.0% vs 61.8%).
What were the additional PRO data?
The rates of completion for the FACT-P in the investigational and control arms at baseline were 76% and 80%, respectively. These respective rates at week 12 were 66% and 71% and were 44% and 56% at week 24. The baseline scores were similar between the 2 arms; the mean scores were 106.7 (SD, 21.6) and 109.4 (SD, 23.0), respectively.
Findings from exploratory descriptive analyses were consistent with the adjusted findings, with similar rates of clinically meaningful worsening of pain by 24 weeks between the investigational (31%) and control (30%) arms. Rates of worsening in pain interference were also similar by this time point (33% vs 34%).
“These PRO findings, together with the previously reported rPFS benefit, support the tolerability and clinical viability of this combination strategy in patients with mCRPC and bone metastases,” McKay and her coauthors wrote in their conclusion. “As radiopharmaceutical combination strategies continue to evolve, including the [phase 3] PEACE‐3 trial [NCT02194842] regimen of radium‐223 plus enzalutamide (Xtandi) and emerging radiopharmaceutical-PARP inhibitor approaches, prospective and adequately powered PRO assessments will be essential to fully characterize the patient experience with these novel treatment combinations.”
References
- McKay RR, Xie W, Ajmera A, et al. Patient-reported outcomes in castration-resistant prostate cancer with bone metastases treated with radium-223 with or without olaparib. Cancer. 2026;132(13):e70496. doi:10.1002/cncr.70496
- McKay RR, Xie W, Ajmera A, et al. Multicenter, randomized, phase II trial of olaparib plus radium-223 versus radium-223 in men with castration-resistant prostate cancer with bone metastases (COMRADE). J Clin Oncol. 2026;44(18):1709-1719. doi:10.1200/JCO-25-02835
