Impact of timing of administration of bone supportive therapy on pain palliation from radium-223

Abstract

Background: Skeletal-related events cause significant morbidity in patients with metastatic castration-resistant prostate cancer. In the ALSYMPCA study, radium-223 (Ra223) was found to provide pain palliation in addition to prolonged survival and reduced skeletal-related events (SREs). Given previous evidence that bisphosphonates impacted pain relief from the radiopharmaceutical samarium-153, we evaluated whether the timing of bone supportive therapy (BST) such as zoledronic acid or denosumab affected pain palliation from Ra223.

Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Patients were evaluable for pain response if they had baseline pain score > 0 and at least 1 pain score documented after Ra223 with pain medication use data. Patients were evaluable for pain flare if they had known baseline pain score and at least 2 pain scores documented after Ra223. Pain response was defined as > 2 point decrease in pain on a 10-point scale; flare was defined as > 2 point increase followed by return to baseline or lower.

Results: Of 65 patients, 22 (34%) received BST. Median number of doses Ra223 was 5 (range 2-6). Fourteen patients were evaluable for pain response and 34 for pain flare. Eighteen patients received concurrent abiraterone (abi) or enzalutamide (enza), and 16 did not. Pain response occurred in 6/6 (100%) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50%) patients who did not receive BST. Pain flare occurred in 6/21 patients (29%) without BST and 2/13 (15%) with BST (p = 0.44). 6/10 (60%) patients with pain response had a decline in alkaline phosphatase (ALP) level, but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline. 6/8 (75%) and 2/18 (11%) patients on abi/enza had pain response and flare respectively, and 4/6 (67%) and 6/16 (38%) patients without concurrent abi/enza had response/flare.

Conclusions: BST within 1 month prior to first Ra223 dose was associated with increased likelihood of pain palliation and might prevent pain flare. Concurrent use of abi/enza was not associated with increased likelihood of pain response but was associated with decreased likelihood of pain flare.

Keywords: Bisphosphonate; Denosumab; Pain flare; Pain response; Prostate cancer; Radium223; Rank ligand; mCRPC.