A Phase II, Nonrandomized Open Trial Assessing Pain Efficacy with Radium-223 in Symptomatic Metastatic Castration-resistant Prostate Cancer

• Published in: Clinical genitourinary cancer 2021-10, Vol.19 (5), p.447-456
• Main Authors: McHugh, Deaglan, Tagawa, Scott, Moryl, Natalie, Milowsky, Matthew, Heller, Glenn, Osborne, Joseph, Rathkopf, Dana, Basch, Ethan, Pandit-Taskar, Neeta, Morris, Michael J.
• Format: Article
• Language: English
• Subjects: Castration-resistant; Patient-reported outcome; Prostate cancer; Radium-223
• ISSN: 1558-7673; 1938-0682
• DOI: 10.1016/j.clgc.2021.04.005

•Bone pain is the leading patient-reported outcome in contemporary trials of advanced prostate cancer; however, preapproval studies have not addressed a therapeutic agent's ability to palliate pain in a manner to use for regulatory approval.•A multicenter, phase II clinical trial examining the use of radium-223 enrolled 29 patients with metastatic castration-resistant prostate cancer and a Brief Pain Inventory score of greater than 3, with primary end point defined as a greater than 30decrease decline in the Brief Pain Inventory score by week 8 and confirmed at week 12•The primary end point was met in 43% of patients, easily satisfying the protocol-defined threshold for expansion to a second phase, but accrual was slow and did not proceed to the second phase.•This prospective trial was the first examining radium-223 in pain palliation using standard doses and contemporary pain end points radium-223, and demonstrated radium-223’s ability to palliate pain in a clinically meaningful manner in nearly one-half of enrolled patients Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach to pain assessment in preapproval trials. No prior trial has examined pain palliation of Radium-223 using standard dosing and contemporary PRO pain-assessment tools. In this multicenter phase II trial, patients with Brief Pain Inventory (BPI) ≥3 were eligible for Radium-223 per its label. Primary endpoint was a 30% decrease in BPI Worst Pain from baseline to Week 8, sustained at Week 12 without escalation of medication on the World Health Organization (WHO) analgesic ladder. Secondary endpoints included changes in Brief Fatigue Inventory (BFI) Worst fatigue and BPI pain interference. If six of 27 subjects (22%) met the primary endpoint, the trial would expand by another 36 subjects. Twenty-nine subjects were accrued. Nine of 29 (31%) subjects met the primary endpoint, with 21 (72%) evaluable for the primary endpoint. Among responders: median worst pain declined 62% (range 36–100) at Week 8 and 63% (range 38–100) at Week 12; median reduction of pain interference with general activity and sleep at Week 12 was 62% (range 18–100) and 53% (range 8–100) respectively; median reduction in worst fatigue of 45% (range 10–85) at Week 12. In the first prospective trial using standard Ra-223 doses, contemporary pain endpoints and PRO collection tools, Ra-223 palliated pain, reduced fatigue, and improved pain interference. The pain response rate easily exceeded the