Quality of life analysis from a multicenter, randomized, phase 2, investigator-initiated ETCTN trial of olaparib + radium-223 versus radium-223 in metastatic castration-resistant prostate cancer with bone metastases (COMRADE).

Abstract

5040 Background: Radium-223 is an α-emitting radioisotope that improves overall survival in men with metastatic castration resistant prostate cancer (mCRPC) and bone metastases (BM). In the ALSYMPCA trial, radium-223 was also associated with improved quality of life (QOL), delayed time to first opioid use, and pain palliation. We previously reported superior radiographic progression free survival (rPFS) with the addition of olaparib to radium-223 in the randomized phase 2 COMRADE study (NCT03317391). We now report patient-reported QOL outcomes from the trial. Methods: Patients were randomized 1:1 to olaparib 200 mg twice daily plus radium-223 (Arm A) or radium-223 alone (Arm B). QOL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory (BPI) at baseline and every 12 weeks. Mixed-effects ANCOVA models assessed treatment effects on QOL changes from baseline, adjusting for baseline score, timepoint, age, and Eastern Cooperative Oncology Group performance status. Least-squares (LS) mean changes were reported for each arm with between-arm differences and 95% confidence intervals. Analysis was limited to patients with baseline and ≥1 post-baseline assessment within 24 weeks. Results: Of 114 treated patients, 74 (65%) were evaluable for QOL analysis (Arm A, n = 40; Arm B, n = 34), including 71 (62%) for FACT-P and 72 (63%) for BPI pain severity and pain interference. Baseline characteristics were well balanced: median age was 70 and 72 years, ECOG PS 1 was present in 60% and 62%, prior docetaxel was received by 55% and 50%, > 20 bone metastases were present in 45% and 47%, and pain medication use at baseline was reported in 60% and 72% of patients in Arms A and B, respectively. There were no significant differences in LS mean change from baseline in FACT-P total score between arms at week 12 (Arm A: -5.09 vs Arm B: -0.23; difference -4.87, 95% CI -13.4 to 3.62) or week 24 (Arm A: -1.41 vs Arm B: -3.20; difference 1.79, 95% CI -8.28 to 11.9). Similarly, no significant between-arm differences were observed in LS mean changes in BPI pain severity at week 12 (difference 0.44, 95% CI -0.44 to 1.33) or week 24 (difference -0.20, 95% CI -1.32 to 0.93). Arm B showed greater improvement in BPI pain interference at week 12 (LS mean change: Arm A +0.21 vs Arm B -0.88; difference 1.09, 95% CI 0.14 to 2.05), but this difference was not sustained at week 24 (difference -0.27, 95% CI -1.37 to 0.82). Conclusions: In this phase 2 trial, the addition of olaparib to radium-223 achieved superior rPFS without significant detriment to patient-reported QOL or pain compared to radium-223 alone, supporting the tolerability of this combination in mCRPC patients with BM. Clinical trial information: NCT03317391 .